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 b ecome highly susceptible to sIg-mediated negative selection, a process best exemplified by tolerance induction. Recent studies with sIg tran sgenic mice have suggested that B cells may become inactivated by tole rogens only after a developmental stage wherein they express low level s of sIgM and during the course of up-regulating their expression of s IgM. To determine whether inactivation of B cells of conventional mice occurs at this or other maturational stages, we have analyzed the rat io of productive vs nonproductive rearrangements of V(H)81X gene segme nts in developmental subsets of adult bone marrow cells. Earlier studi es had demonstrated that cells whose productively rearranged H chain V region contained a V(H)81X gene segment were selectively disfavored b oth during pre-B cell development and subsequent to sIg expression. Co ntrary to the expectations for elimination by tolerance, no decrease i n the proportion of cells expressing productive rearrangements of V(H) 81X was observed as cells matured from the sIgM(low) to the sIgM(high) maturational stage. However, a significant decrease in the proportion of productively rearranged V(H)81X gene segments was observed followi ng the transition from sIg(-) pre-B cells to sIgM(low) immature B cell s. Additionally, the proportion of productively rearranged V(H)81X gen e segments was significantly higher in sIgM(high) bone marrow cells th an in splenic B cells. These findings demonstrate that B cells are sus ceptible to H chain-specific elimination at two developmental stages o ther than that wherein B cells are generally assumed to be negatively selected by tolerance.