Pathway Human Homo sapiens

Immunoglobulin maturation

R-HSA-9938026 in Reactome release 97: under Adaptive Immune System, with 357 genes placed in it by the mapping files and 1 child pathway in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-9938026 (mouse), R-RNO-9938026 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-9938026.1
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2026-06-17
Events inside: 1, counted from the record

In humans, three loci encode immunoglobulin chains: the IGH locus encodes the heavy chain, the IGK locus encodes the kappa light chain, and the IGL locus encodes the lambda light chain. In the germline, the three loci each contain many alternative gene segments that are capable of producing the variable region of the immunoglobulin (reviewed in Pennell et al. 2023). The heavy chain locus (IGH) also contains nine alternative C-terminal segments capable of producing the constant regions of the nine classes of immunoglobulins: IgM, IgD, IgG3, IgG1, IgA1, IgG2, IgG4, IgE, and IgA2 (listed in order of their occurrence on the chromosome, Xu et al. 2012).

In the B cell lineage in the bone marrow, the three immunoglobulin loci are recombined to produce specific variable regions that can recognize specific antigens (reviewed in Christie et al. 2022). A specific heavy chain is produced by recombination among about 57 variable (V) segments, 23 diversity (D) segments, and 6 joining (J) segments, a process called VDJ recombination (reviewed in Mikocziova et al. 2021). The light chains are produced by recombination between 41 (IGK) or 34 (IGL) V segments and 5 J segments, a process called VJ recombination (reviewed in Mikocziova et al. 2021). The term V(D)J recombination refers to recombination at all of the three loci. V(D)J recombination is initiated by DNA cleavage catalyzed by the RAG1:RAG2 recombinase complex at sites flanking the V, D (if present), and J segments followed by repair of double-strand breaks (reviewed in Schatz and Ji 2011, Yu 2022, Christie et al. 2022).

The initial class of the recombined heavy chain is usually IgM, as the M-type C-terminal segment is the most upstream in the array of C-terminal segments at the IGH locus. In germinal centers (reviewed in Victora and Nussenzweig 2022), a process called class switch recombination (CSR) occurs in which the region encoding the variable domain is recombinationally joined to a gene segment encoding the C-terminal constant domain (reviewed in Xu et al. 2012, Matthews et al. 2014, Liu et al. 2024). Activation-induced cytosine deaminase (AICDA, also called AID) deaminates cytidine residues at the Cmu site upstream of the M-type segment and at specific sites, switch regions, flanking the downstream C-terminal segments (reviewed in Matthews et al. 2014, Yu 2022). DNA repair enzymes act on the resulting G:U mismatches to create and resolve double-strand breaks. This produces recombination events that eliminate the M-type segment and in some cases additional segments to generate one of the eight other class types.

The affinity of immunoglobulins for antigens is further enhanced by somatic hypermutation and affinity selection in germinal centers (reviewed in Haberman et al. 2019, Young and Brink 2021, Victora and Nussenzweig 2022). Functionally, higher-affinity B cells are selected based on their ability to capture antigen from follicular dendritic cells (reviewed in Tolar 2017, Papa and Vinuesa 2018, Nakagawa and Calado 2021). The B cell then proteolytically processes the antigen and displays antigen peptides on MHC II complexes to follicular helper T cells, which secrete helper cytokines (principally IL4 and IL21) to maintain the viability of the B cell and cause it to proliferate (reviewed in Crotty et al. 2019). A program of somatic hypermutation is triggered in which AICDA deaminates cytidine residues in the variable regions of immunoglobulin loci (reviewed in Yu 2022). The deamination and subsequent error-prone repair produce mutations (reviewed in Pilzecker and Jacobs 2019, Hao et al. 2024). The mutant immunoglobulins are then re-selected for affinity as described above.

Literature Reactome attaches

Germinal center B cell initiation, GC maturation, and the coevolution of its stromal cell nichesImmunol Rev, 2019, vol. 288, p. 10-27PubMed 30874342
The unique biology of germinal center B cellsImmunity, 2021, vol. 54, p. 1652-1664PubMed 34380063
Immunoglobulin class-switch DNA recombination: induction, targeting and beyondNat Rev Immunol, 2012, vol. 12, p. 517-31PubMed 22728528
Positive Selection in the Light Zone of Germinal CentersFront Immunol, 2021, vol. 12, p. 661678PubMed 33868314
Mutating for Good: DNA Damage Responses During Somatic HypermutationFront Immunol, 2019, vol. 10, p. 438PubMed 30915081
Molecular mechanisms of DNA lesion and repair during antibody somatic hypermutationSci China Life Sci, 2024, vol. 67, p. 2344-2353PubMed 39048716
AID function in somatic hypermutation and class switch recombinationActa Biochim Biophys Sin (Shanghai), 2022, vol. 54, p. 759-766PubMed 35975606

Reactome's record lists 14 orthologous events, R-RNO-9938026 (Rattus norvegicus), R-MMU-9938026 (Mus musculus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-04 ET · Reactome pathway browser"Immunoglobulin maturation". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9938026 with StableID: R-HSA-9938026.1 (accessed 2026-10-04 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 357 genes in this human pathway; showing 201 to 300, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 3 of 4
Gene	Authority id	Mapping file id	Evidence codes
GeneKIF22	AuthorityHGNC:6391	Mapping file id3835 NCBI file	EvidenceTAS
GeneKIF23	AuthorityHGNC:6392	Mapping file id9493 NCBI file	EvidenceTAS
GeneKIF26A	AuthorityHGNC:20226	Mapping file id26153 NCBI file	EvidenceTAS
GeneKIF2A	AuthorityHGNC:6318	Mapping file id3796 NCBI file	EvidenceTAS
GeneKIF2B	AuthorityHGNC:29443	Mapping file id84643 NCBI file	EvidenceTAS
GeneKIF2C	AuthorityHGNC:6393	Mapping file id11004 NCBI file	EvidenceTAS
GeneKIF3A	AuthorityHGNC:6319	Mapping file id11127 NCBI file	EvidenceTAS
GeneKIF3B	AuthorityHGNC:6320	Mapping file id9371 NCBI file	EvidenceTAS
GeneKIF3C	AuthorityHGNC:6321	Mapping file id3797 NCBI file	EvidenceTAS
GeneKIF4A	AuthorityHGNC:13339	Mapping file id24137 NCBI file	EvidenceTAS
GeneKIF4B	AuthorityHGNC:6322	Mapping file id285643 NCBI file	EvidenceTAS
GeneKIF5A	AuthorityHGNC:6323	Mapping file id3798 NCBI file	EvidenceTAS
GeneKIF5B	AuthorityHGNC:6324	Mapping file id3799 NCBI file	EvidenceTAS
GeneKIFAP3	AuthorityHGNC:17060	Mapping file id22920 NCBI file	EvidenceTAS
GeneKLC1	AuthorityHGNC:6387	Mapping file id3831 NCBI file	EvidenceTAS
GeneKLC2	AuthorityHGNC:20716	Mapping file id64837 NCBI file	EvidenceTAS
GeneKLC3	AuthorityHGNC:20717	Mapping file id147700 NCBI file	EvidenceTAS
GeneKLC4	AuthorityHGNC:21624	Mapping file id89953 NCBI file	EvidenceTAS
GeneKMT2C	AuthorityHGNC:13726	Mapping file id58508 NCBI file	EvidenceIEA
GeneKMT2D	AuthorityHGNC:7133	Mapping file id8085 NCBI file	EvidenceIEA
GeneLEO1	AuthorityHGNC:30401	Mapping file id123169 NCBI file	EvidenceIEA
GeneMAD2L2	AuthorityHGNC:6764	Mapping file id10459 NCBI file	EvidenceIEA, TAS
GeneMAF	AuthorityHGNC:6776	Mapping file id4094 NCBI file	EvidenceIEA
GeneMAFK	AuthorityHGNC:6782	Mapping file id7975 NCBI file	EvidenceIEA
GeneMCM3AP	AuthorityHGNC:6946	Mapping file id8888 NCBI file	EvidenceTAS
GeneMEF2B	AuthorityHGNC:6995	Mapping file id100271849 NCBI file	EvidenceIEA
GeneMLH1	AuthorityHGNC:7127	Mapping file id4292 NCBI file	EvidenceTAS
GeneMLLT1	AuthorityHGNC:7134	Mapping file id4298 NCBI file	EvidenceIEA
GeneMLLT3	AuthorityHGNC:7136	Mapping file id4300 NCBI file	EvidenceIEA
GeneMPHOSPH6	AuthorityHGNC:7214	Mapping file id10200 NCBI file	EvidenceIEA
GeneMSH2	AuthorityHGNC:7325	Mapping file id4436 NCBI file	EvidenceTAS
GeneMSH6	AuthorityHGNC:7329	Mapping file id2956 NCBI file	EvidenceTAS
GeneMYB	AuthorityHGNC:7545	Mapping file id4602 NCBI file	EvidenceIEA
GeneMYH9	AuthorityHGNC:7579	Mapping file id4627 NCBI file	EvidenceIEA
GeneNCOA6	AuthorityHGNC:15936	Mapping file id23054 NCBI file	EvidenceIEA
GeneNELFA	AuthorityHGNC:12768	Mapping file id7469 NCBI file	EvidenceIEA
GeneNELFB	AuthorityHGNC:24324	Mapping file id25920 NCBI file	EvidenceIEA
GeneNELFCD	AuthorityHGNC:15934	Mapping file id51497 NCBI file	EvidenceIEA
GeneNELFE	AuthorityHGNC:13974	Mapping file id7936 NCBI file	EvidenceIEA
GeneNFKB1	AuthorityHGNC:7794	Mapping file id4790 NCBI file	EvidenceIEA
GeneNFKB2	AuthorityHGNC:7795	Mapping file id4791 NCBI file	EvidenceIEA
GeneOSBPL1A	AuthorityHGNC:16398	Mapping file id114876 NCBI file	EvidenceTAS
GenePAF1	AuthorityHGNC:25459	Mapping file id54623 NCBI file	EvidenceIEA
GenePAGR1	AuthorityHGNC:28707	Mapping file id79447 NCBI file	EvidenceIEA
GenePAX5	AuthorityHGNC:8619	Mapping file id5079 NCBI file	EvidenceIEA
GenePAXIP1	AuthorityHGNC:8624	Mapping file id22976 NCBI file	EvidenceIEA
GenePCNA	AuthorityHGNC:8729	Mapping file id5111 NCBI file	EvidenceIEA, TAS
GenePMS2	AuthorityHGNC:9122	Mapping file id5395 NCBI file	EvidenceTAS
GenePOLD2	AuthorityHGNC:9176	Mapping file id5425 NCBI file	EvidenceIEA, TAS
GenePOLD3	AuthorityHGNC:20932	Mapping file id10714 NCBI file	EvidenceIEA, TAS
GenePOLH	AuthorityHGNC:9181	Mapping file id5429 NCBI file	EvidenceIEA, TAS
GenePOLI	AuthorityHGNC:9182	Mapping file id11201 NCBI file	EvidenceIEA, TAS
GenePOLR2A	AuthorityHGNC:9187	Mapping file id5430 NCBI file	EvidenceIEA
GenePOLR2B	AuthorityHGNC:9188	Mapping file id5431 NCBI file	EvidenceIEA
GenePOLR2C	AuthorityHGNC:9189	Mapping file id5432 NCBI file	EvidenceIEA
GenePOLR2D	AuthorityHGNC:9191	Mapping file id5433 NCBI file	EvidenceIEA
GenePOLR2E	AuthorityHGNC:9192	Mapping file id5434 NCBI file	EvidenceIEA
GenePOLR2F	AuthorityHGNC:9193	Mapping file id5435 NCBI file	EvidenceIEA
GenePOLR2G	AuthorityHGNC:9194	Mapping file id5436 NCBI file	EvidenceIEA
GenePOLR2H	AuthorityHGNC:9195	Mapping file id5437 NCBI file	EvidenceIEA
GenePOLR2I	AuthorityHGNC:9196	Mapping file id5438 NCBI file	EvidenceIEA
GenePOLR2J	AuthorityHGNC:9197	Mapping file id5439 NCBI file	EvidenceIEA
GenePOLR2K	AuthorityHGNC:9198	Mapping file id5440 NCBI file	EvidenceIEA
GenePOLR2L	AuthorityHGNC:9199	Mapping file id5441 NCBI file	EvidenceIEA
GenePRDM1	AuthorityHGNC:9346	Mapping file idENSG00000057657 Ensembl file	EvidenceIEA
GeneRAB7A	AuthorityHGNC:9788	Mapping file id7879 NCBI file	EvidenceTAS
GeneRACGAP1	AuthorityHGNC:9804	Mapping file id29127 NCBI file	EvidenceTAS
GeneRBBP5	AuthorityHGNC:9888	Mapping file id5929 NCBI file	EvidenceIEA
GeneRELA	AuthorityHGNC:9955	Mapping file id5970 NCBI file	EvidenceIEA
GeneRELB	AuthorityHGNC:9956	Mapping file id5971 NCBI file	EvidenceIEA
GeneREV1	AuthorityHGNC:14060	Mapping file id51455 NCBI file	EvidenceIEA, TAS
GeneREV3L	AuthorityHGNC:9968	Mapping file id5980 NCBI file	EvidenceIEA, TAS
GeneRFC1	AuthorityHGNC:9969	Mapping file id5981 NCBI file	EvidenceIEA, TAS
GeneRFC2	AuthorityHGNC:9970	Mapping file id5982 NCBI file	EvidenceIEA, TAS
GeneRFC3	AuthorityHGNC:9971	Mapping file id5983 NCBI file	EvidenceIEA, TAS
GeneRFC4	AuthorityHGNC:9972	Mapping file id5984 NCBI file	EvidenceIEA, TAS
GeneRFC5	AuthorityHGNC:9973	Mapping file id5985 NCBI file	EvidenceIEA, TAS
GeneRILP	AuthorityHGNC:30266	Mapping file id83547 NCBI file	EvidenceTAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceIEA, TAS
GeneRTF1	AuthorityHGNC:28996	Mapping file id23168 NCBI file	EvidenceIEA
GeneSH2D1A	AuthorityHGNC:10820	Mapping file id4068 NCBI file	EvidenceIEA
GeneSKIC8	AuthorityHGNC:30300	Mapping file id80349 NCBI file	EvidenceIEA
GeneSLAMF6	AuthorityHGNC:21392	Mapping file id114836 NCBI file	EvidenceIEA
GeneSMARCA2	AuthorityHGNC:11098	Mapping file id6595 NCBI file	EvidenceIEA
GeneSMARCA4	AuthorityHGNC:11100	Mapping file id6597 NCBI file	EvidenceIEA
GeneSMARCB1	AuthorityHGNC:11103	Mapping file id6598 NCBI file	EvidenceIEA
GeneSMARCC1	AuthorityHGNC:11104	Mapping file id6599 NCBI file	EvidenceIEA
GeneSMARCC2	AuthorityHGNC:11105	Mapping file id6601 NCBI file	EvidenceIEA
GeneSMARCD1	AuthorityHGNC:11106	Mapping file id6602 NCBI file	EvidenceIEA
GeneSMARCD2	AuthorityHGNC:11107	Mapping file id6603 NCBI file	EvidenceIEA
GeneSMARCD3	AuthorityHGNC:11108	Mapping file id6604 NCBI file	EvidenceIEA
GeneSMARCE1	AuthorityHGNC:11109	Mapping file id6605 NCBI file	EvidenceIEA
GeneSPTBN2	AuthorityHGNC:11276	Mapping file id6712 NCBI file	EvidenceTAS
GeneSS18	AuthorityHGNC:11340	Mapping file id6760 NCBI file	EvidenceIEA
GeneSS18L1	AuthorityHGNC:15592	Mapping file id26039 NCBI file	EvidenceIEA
GeneSSRP1	AuthorityHGNC:11327	Mapping file id6749 NCBI file	EvidenceIEA
GeneSTAT3	AuthorityHGNC:11364	Mapping file id6774 NCBI file	EvidenceIEA, TAS
GeneSTAT6	AuthorityHGNC:11368	Mapping file id6778 NCBI file	EvidenceIEA
GeneSUPT16H	AuthorityHGNC:11465	Mapping file id11198 NCBI file	EvidenceIEA
GeneSUPT4H1	AuthorityHGNC:11467	Mapping file id6827 NCBI file	EvidenceIEA

Evidence codes on this page: IEA, TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Adaptive Immune SystemR-HSA-12802181,149 genes

Children

Affinity selection of immunoglobulinsR-HSA-9938027357 genes

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.