Affiliation To Mature B Cell Repertoire And Positive Selection Can Be Separated In Two Distinct Processes

Using an 'oligoclonal' model, we have previously shown that mice transgenic for a mu chain (H3) and deficient for kappa chain expression display a mature B cell repertoire largely dominated by the H3/lambda 1 pair, while the four H3/lambda available combinations can be observed in the immature B cell compartment. This led us to propose the existence of a positive selection process. To test this hypothesis, we have introduced the SJL lambda locus coding for a defective lambda 1 chain (lambda 1(s)) that creates a dysfunctional Ig receptor complex during a cell differentiation. Our results show that the lambda 1(s) defect impairs the development of mature B cells when the H3-mu transgene insert is present in the hemizygous state. This suggests that the Gly --> Val substitution present in the C(lambda)1(s) chain at position 155 is sufficient to abrogate the selection of the H3/lambda 1 pair. Unexpectedly, when the H3-mu transgene array is present in a homozygous state in lambda 1(s) mice but not in 'wild-type' lambda(1) mice (lambda 1(+)), a significant number of mature B cells expressing all H3/lambda combinations can be developed. These results indicate that the overriding H3/lambda 1 dominance observed in lambda 1(+) mice is due to a positive selection process and not to a negative selection of other H3/lambda combinations. They also show that the export of B cells to the periphery can be controlled by the expression of the mu chain.