期刊
INTERNATIONAL IMMUNOLOGY
卷 12, 期 6, 页码 767-775出版社
OXFORD UNIV PRESS
DOI: 10.1093/intimm/12.6.767
关键词
B lymphocytes; Ig; selection; somatic hypermutation; VDJ rearrangement
类别
资金
- PHS HHS [A131229] Funding Source: Medline
Analysis of the V(H)DJ(H) repertoire of peripheral blood IgM(+) B cells from a patient with X-linked hyper-IgM syndrome (X-HIgM) was undertaken to determine whether the distribution of V-H families in the productive repertoire might be regulated by in vivo CD40-CD154 interactions. The distribution of V-H genes in the non-productive repertoire of IgM(+) B cells was comparable in X-HIgM and normals. Unlike the normal productive V-H repertoire, however, in the X-HIgM patient the V(H)4 family was found at almost the same frequency as the V(H)3 family. This reflected a diminution in the positive selection of the V(H)3 family observed in normals and the imposition of positive selection of the V(H)4 family in the X-HIgM patient. Unique among the V(H)3 genes, V(H)3-23/DP-47 was positively selected in both normals and the X-HIgM patient. No major differences in the usage of J(H) or D segments or the complementarity-determining region (CDR) 3 were noted, although the foreshortening of the CDR3 noted in the mutated V-H rearrangements of normals was absent in the X-HIgM patient. Finally, a minor degree of somatic hypermutation was noted in the X-HIgM patient. These results have suggested that specific influences on the composition of the V-H repertoire in normals require CD40-CD154 interactions.
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