TY - JOUR
T1 - The influence of CD40-CD154 interactions on the expressed human V(H) repertoire
T2 - Analysis of V(H) genes expressed by individual B cells of a patient with X-linked hyper-IgM syndrome
AU - Brezinschek, Hans Peter
AU - Dörner, Thomas
AU - Monson, Nancy L.
AU - Brezinschek, Ruth I.
AU - Lipsky, Peter E.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - B lymphocytes
KW - Ig
KW - Selection
KW - Somatic hypermutation
KW - VDJ rearrangement
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U2 - 10.1093/intimm/12.6.767
DO - 10.1093/intimm/12.6.767
M3 - Article
C2 - 10837404
AN - SCOPUS:0343893635
SN - 0953-8178
VL - 12
SP - 767
EP - 775
JO - International Immunology
JF - International Immunology
IS - 6
ER -