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PMID: 11158612 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

CD40-CD40L independent Ig gene hypermutation suggests a second B cell diversification pathway in humans.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 3 ·2001-01-30 ·Pages 1166-70

Weller S, Faili A, Garcia C, Braun MC, Le Deist F F, de Saint Basile G G, Hermine O, Fischer A, Reynaud CA, Weill JC

Abstract

Somatically mutated IgM(+)-only and IgM(+)IgD(+)CD27(+) B lymphocytes comprise approximately 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.

MeSH Terms
Adolescent Adult Alternative Splicing B-Lymphocyte Subsets/immunology B-Lymphocytes/immunology CD40 Antigens/genetics,immunology CD40 Ligand/genetics,immunology Child Child, Preschool Codon, Terminator Fetal Blood/immunology Gene Rearrangement Genes, Immunoglobulin Humans Immunoglobulin A/blood Immunoglobulin D/genetics Immunoglobulin G/blood Immunoglobulin M/blood,genetics Immunologic Deficiency Syndromes/blood,genetics,immunology Infant, Newborn Mutation Reference Values Sequence Deletion
Chemicals
CD40 Antigens Codon, Terminator Immunoglobulin A Immunoglobulin D Immunoglobulin G Immunoglobulin M CD40 Ligand
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Weller S
Institut National de la Santé et de la Recherche Médicale U373, Faculté de Médecine Necker-Enfants Malades, 156, Rue de Vaugirard, 75730 Paris Cedex 15, France.
Faili A
Garcia C
Braun M C
Le Deist F F
de Saint Basile G G
Hermine O
Fischer A
Reynaud C A
Weill J C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.98.3.1166
Published
2001-01-30
Pages
1166-70
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC14726
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.98.3.1166 PMC Full Text View journal details
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