Frequency of VH81x usage during B cell development: initial decline in usage is independent of Ig heavy chain cell surface expression.
B cell development is marked by changes in the pattern of VH segment utilization. B cell precursors characteristically utilize a restricted set of VH segments, while mature B cell populations use a wide range of VH segments. VH81x is an example of a VH segment that is highly utilized in B cell precursors, but rarely utilized in mature B cells. We have developed an assay that allows us to determine the proportion of VDJH rearrangements that utilize the VH81x segment in DNA from selected populations of developing B cells. Consistent with previous observations, it was found that VH81x is utilized at a remarkably high frequency in primary B cell progenitors. The extent of overutilization was found to be identical during fetal and adult B cell development. Phenotypic analyses demonstrated that the decline in VH81x utilization begins at a stage before the expression of IgM on the cell surface and continues through later stages of B cell development. Strikingly, mutant mice that cannot express Ig heavy chain on the cell surface displayed a drop in VH81x utilization during both fetal and adult B cell development. Together, these data suggest that mechanisms other than cellular selection play an important role in determining the shift in VH segment utilization during B cell development.
Marshall
A J
AJ
Wellesley Hospital Research Institute, Toronto, Ontario, Canada.
Wu
G E
GE
Paige
G J
GJ
D000818:Animals; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D002461:Cell Line, Transformed; D005314:Embryonic and Fetal Development / Q000276:immunology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000276:immunology; D005865:Gestational Age; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics*
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell