Frequency of VH81x usage during B cell development: initial decline in usage is independent of Ig heavy chain cell surface expression.

摘要

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.