AVAILABLE LAMBDA B-CELL REPERTOIRE IN THE MOUSE - EVIDENCE OF POSITIVE SELECTION BY ENVIRONMENTAL-FACTORS

We have recently shown that, from two BALB/c mice treated with rabbit anti-Clambda2/Clambda3 antibodies coupled to lipopolysaccharide, variable heavy chain (V(H)) family repertoires associated with lambda2 or lambda3 light chains can differ from one lambda subtype to another and from one individual mouse to another. Indeed, 4 out of 6 lambda2 (VxJ2) hybridomas from one mouse preferentially expressed the V(H) 10 family while 3 out of 8 lambda2 (V2J2) and 5 out of 8 lambda2 (VxJ2) hybridomas from a second mouse preferentially expressed the S107 and VGAM3.8 V(H) families, respectively. In this report, we describe the structural basis of such preferential pairings by sequence analysis of the 12 lambda2 hybridomas. The sequence comparison of their V(H) regions show that each preferential association of a V(H) family to one Vlambda region is restricted to the use of a single member or very closely related members inside a V(H) family and that a great variability of CDR3 of heavy chain is observed. We, therefore, suggest that environmental factors can modify the available lambda B cell repertoire through a positive selection of particular V(H)/Vlambda pairings. Moreover, our data support that this selection does not require clonal expansion and punctual somatic mutation.