Frequency of VH81x usage during B cell development: initial decline in usage is independent of Ig heavy chain cell surface expression
Marshall, A.J.; Wu, G.E.; Paige, G.J.
Journal of Immunology 156(6): 2077-2084
1996
ISSN/ISBN: 0022-1767 PMID: 8690895 Document Number: 456240
B cell development is marked by changes in the pattern of V-H segment utilization. B cell precursors characteristically utilize a restricted set of V-H segments, while mature B cell populations use a wide range of V-H segments. V-H81x is an example of a V-H 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 VDJ, rearrangements that utilize the V-H81x segment in DNA from selected populations of developing B cells. Consistent with previous observations, it was found that V-H81x 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 V-H81x 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 V-H81x 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 V-H segment utilization during B cell development.