The influence of CD40–CD154 interactions on the expressed human VH repertoire: analysis of VH genes expressed by individual B cells of a patient with X-linked hyper-IgM syndrome
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
... 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.