International Immunology, Vol. 12, No. 6, 767-775,
June 2000
© 2000 Japanese Society for Immunology
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
Department of Internal Medicine and Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas TX 75235, USA
Correspondence to: P. E. Lipsky
Analysis of the VHDJH 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 VH families in the productive repertoire might be regulated by in vivo CD40–CD154 interactions. The distribution of VH genes in the non-productive repertoire of IgM+ B cells was comparable in X-HIgM and normals. Unlike the normal productive VH repertoire, however, in the X-HIgM patient the VH4 family was found at almost the same frequency as the VH3 family. This reflected a diminution in the positive selection of the VH3 family observed in normals and the imposition of positive selection of the VH4 family in the X-HIgM patient. Unique among the VH3 genes, VH3-23/DP-47 was positively selected in both normals and the X-HIgM patient. No major differences in the usage of JH or D segments or the complementarity-determining region (CDR) 3 were noted, although the foreshortening of the CDR3 noted in the mutated VH 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 VH repertoire in normals require CD40–CD154 interactions.
Keywords: B lymphocytes, Ig, selection, somatic hypermutation, VDJ rearrangement
1 Present address: Medical University Clinic Graz, Auenbruggerplatz 15, 8036 Graz, Austria
Transmitting editor: A. Fischer
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