CD40-CD40L Independent Ig Gene Hypermutation Suggests a Second B Cell Diversification Pathway in Humans

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 3; pp. 1166 - 1170
• Main Authors: Weller, Sandra, Faili, Ahmad, Garcia, Corinne, Braun, Moritz C., Le Deist, Françoise, Geneviève de Saint Basile, Hermine, Olivier, Fischer, Alain, Reynaud, Claude-Agnès, Weill, Jean-Claude
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 30-01-2001; National Acad Sciences; The National Academy of Sciences
• Subjects: Adolescent; Adult; Alternative Splicing; B lymphocytes; B-Lymphocyte Subsets - immunology; B-Lymphocytes - immunology; Biological Sciences; CD40 antigen; CD40 Antigens - genetics; CD40 Antigens - immunology; CD40 Ligand - genetics; CD40 Ligand - immunology; CD40L antigen; CD40L gene; CD40L protein; Child; Child, Preschool; Children; Codon, Terminator; Cord blood; Exons; Fetal Blood - immunology; Gene Rearrangement; Genes, Immunoglobulin; Genetic mutation; Humans; Immunoglobulin A - blood; Immunoglobulin D - genetics; Immunoglobulin G - blood; Immunoglobulin M - blood; Immunoglobulin M - genetics; Immunologic Deficiency Syndromes - blood; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - immunology; Infant, Newborn; Memory; Mutation; Natural killer cells; Polymerase chain reaction; Population control; Reference Values; Sequence Deletion; T lymphocytes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.98.3.1166

Somatically mutated IgM+-only and IgM+IgD+CD27+B lymphocytes comprise ≈25% of the human peripheral B cell pool. These cells phenotypically resemble class-switched B cells and have therefore been classified as postgerminal center memory B cells. X-linked hyper IgM patients have a genetic defect characterized by a mutation of the CD40L gene. These patients, who do not express a functional CD40 ligand, cannot switch Ig isotypes and do not form germinal centers and memory B cells. We report here that an IgM+IgD+CD27+B cell subset with somatically mutated Ig receptors is generated in these patients, implying that these cells expand and diversify their Ig receptors in the absence of classical cognate T-B collaboration. The presence of this sole subset in the absence of IgM+-only and switched CD27+memory B cells suggests that it belongs to a separate diversification pathway.