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-C lambda 2/C lambda 3 antibodies coupled to lipopolysaccharide, variable heavy chain (VH) family repertoires associated with lambda 2 or lambda 3 light chains can differ from one lambda subtype to another and from one individual mouse to another. Indeed, 4 out of 6 lambda 2 (VxJ2) hybridomas from one mouse preferentially expressed the VH10 family while 3 out of 8 lambda 2 (V2J2) and 5 out of 8 lambda 2 (VxJ2) hybridomas from a second mouse preferentially expressed the S107 and VGAM3.8 VH families, respectively. In this report, we describe the structural basis of such preferential pairings by sequence analysis of the 12 lambda 2 hybridomas. The sequence comparison of their VH regions show that each preferential association of a VH family to one V lambda region is restricted to the use of a single member or very closely related members inside a VH 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 VH/V lambda pairings. Moreover, our data support that this selection does not require clonal expansion and punctual somatic mutation.