Journal
MOLECULAR IMMUNOLOGY
Volume 44, Issue 9, Pages 2173-2183Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2006.11.020
Keywords
human; B cells; antibodies; memory; repertoire development
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Funding
- NCI NIH HHS [P30 CA068485, P30 CA68485] Funding Source: Medline
- NCRR NIH HHS [M01 RR000095, M01 RR-00095] Funding Source: Medline
- NIAID NIH HHS [R01 AI-57933, T32 AI-07474, T32 AI007474, R01 AI057933] Funding Source: Medline
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Memory B cells and the antibodies they encode are important for protective immunity against infectious pathogens. Characterization of naive and memory B cell antibody repertoires will elucidate the molecular basis for the generation of antibody diversity in human B cells and the optimization of antibody structures that bind microbial antigens. In this study we aimed to investigate the influence of antigenic selection on the antibody genes of the two CD27(+) memory B cell subsets, comparing them with the naive repertoire in CD27(-) cells. We analyzed and compared the Ig heavy chain gene transcripts in three recently defined circulating naive and memory B cell subsets (CD19(+)IgD(+)CD27(-) [naive], CD19(+)IgD(+)CD27(-) [un-class-switched memory] or CD19(+)IgD(-)CD27(+) [class-switched memory]) at the single cell level. We found similar biased patterns of variable, diversity and joining heavy chain gene usages in all three groups of cells. CD19(+)IgD(-)CD27(+) memory B cells harbored as diverse an antibody gene repertoire as CD19(+)IgD(-)CD27(+) memory B cells. Interestingly, CD19(+)IgD(-)CD27(+) memory B cells possessed a lower frequency of somatic mutations, a higher incidence of exonuclease activity at the 3' end of D regions, and a lower frequency of N and P nucleotide additions at both V-H-D and D-J(H) junctions of CDR3 regions compared to CD19(+)IgD(-)CD27(+) memory B cells. These data suggest distinct functional mechanisms underlying selection of this unique subset of un-class-switched memory B cells. (c) 2006 Elsevier Ltd. All rights reserved.
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