VARIOUS V-J REARRANGEMENT EFFICIENCIES SHAPE THE MOUSE-LAMBDA B-CELL REPERTOIRE

The diversity of the B cell repertoire of C kappa knockout mice is limited by the expression of four lambda light chain types. Among the spleen B cells, lambda 1 is expressed by the majority (58%) of cells, and lambda 3 by the minority (8%), while lambda 2(V2) and lambda 2(Vx) are expressed in intermediate quantities (18% and 16%, respectively). To assess the influence of mechanistic pressures on the lambda subtype distribution, the proportions of the different lambda rearrangements were determined in various B cell subpopulations divided on the basis of the lambda subtype expressed, and the V lambda J lambda junction sequences were studied at different steps of B cell differentiation (pre-B, immature and mature B cells). The data show that (1) the ratio of productive/non-productive VJ junctions is determined by the nature of the lambda segments that are rearranged as can be observed in the pre-B cells, (2) V1-J1 nonproductive rearrangements are often found in the lambda 1-negative B cells in the periphery and (3) V1J3 junctions are often non-productive regardless of the nature of the cells analyzed. Our results, therefore, suggest that a strong probability of initiating a V1-J1 rearrangement and a weak probability of giving a productive V1J3 junction are responsible for the lambda 1 dominance and the lambda 3 underexpression, respectively The intermediate proportion of lambda 2(V2) subtype is most likely due to a probability of obtaining a productive joint that is better than that for V1J3 and a probability of initiating a rearrangement that is lower than that for V1J1. However, the lambda 2(Vx) cell proportion cannot be determined only by these parameters.