B-1A, B-1B AND B-2 B-CELLS DISPLAY UNIQUE V(H)DJ(H) REPERTOIRES FORMED AT DIFFERENT STAGES OF ONTOGENY AND UNDER DIFFERENT SELECTION PRESSURES

Analyses of V(H)DJ(H) rearrangements isolated from murine peritoneal B-1a cells (CD5(+), IgM(hi), B220(lo)), peritoneal B-1b cells (CD5(-), IgM(hi), B220(lo)), and conventional splenic B cells provide evidence that a unique repertoire of V-H regions is displayed by each of these B-cell subsets. The B-1a subset is characterized by a low N-region diversity, by a high frequency of sequence homologies in the V-H-D and D-J(H) junctions, and by a limited exonuclease nibbling of the terminals of the joining gene segments. Through expansion in ageing mice, B-1a clones with these properties are favoured. B-1b cells are similar to conventional B-2 cells with respect to N-region diversity, but are unique in terms of D gene expression. Thus, while most murine pre-B and B cells preferentially use DSP and DFL gene segments in a given reading frame (RF1), B-1b cells frequently express D genes in another reading frame (RF2). Together, these findings provide structural evidence for a model where B-1a, B-1b and B-2 cells are produced by separate progenitors that are active at different stages of ontogeny.