Heavy chain V gene-specific elimination of B cells during the pre-B cell to B cell transition.

As developing B cells acquire their surface Ig (sIg) receptors, they become highly susceptible to sIg-mediated negative selection, a process best exemplified by tolerance induction. Recent studies with sIg transgenic mice have suggested that B cells may become inactivated by tolerogens only after a developmental stage wherein they express low levels of sIgM and during the course of up-regulating their expression of sIgM. To determine whether inactivation of B cells of conventional mice occurs at this or other maturational stages, we have analyzed the ratio of productive vs nonproductive rearrangements of VH81X gene segments in developmental subsets of adult bone marrow cells. Earlier studies had demonstrated that cells whose productively rearranged H chain V region contained a VH81X gene segment were selectively disfavored both during pre-B cell development and subsequent to sIg expression. Contrary to the expectations for elimination by tolerance, no decrease in the proportion of cells expressing productive rearrangements of VH81X was observed as cells matured from the sIgMlow to the sIgMhigh maturational stage. However, a significant decrease in the proportion of productively rearranged VH81X gene segments was observed following the transition from sIg- pre-B cells to sIgMlow immature B cells. Additionally, the proportion of productively rearranged VH81X gene segments was significantly higher in sIgMhigh bone marrow cells than in splenic B cells. These findings demonstrate that B cells are susceptible to H chain-specific elimination at two developmental stages other than that wherein B cells are generally assumed to be negatively selected by tolerance.