B-1a, B-1b and B-2 B cells display unique VHDJH repertoires formed at different stages of ontogeny and under different selection pressures.

Abstract

Analyses of VHDJH rearrangements isolated from murine peritoneal B‐1a cells (CD5+, IgMhi, B220lo), peritoneal B‐1b cells (CD5‐, IgMhi, B220lo), and conventional splenic B cells provide evidence that a unique repertoire of VH 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 VH‐D and D‐JH 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.

Analysis of the human VH gene repertoire. Differential effects of selection and somatic hypermutation on human peripheral CD5(+)/IgM+ and CD5(-)/IgM+ B cells.

“…The analysis of genomic DNA from CD5 ϩ and CD5 Ϫ B cell subsets revealed no significant differences in the distribution of V H , D and J H gene segments, nor in the composition of the CDR3. In the mouse, it had been reported that CD5 ϩ or B-1 B cells resemble the fetal repertoire with respect to the complexity of the CDR3 (46). This difference appears to be related to species-dependent variations in the recombination machinery since the CDR3 profiles of CD5 ϩ and CD5 Ϫ B cells observed in the current analysis were comparable and similar to results reported for human cord blood CD5 ϩ and CD5 Ϫ B cells (17).…”

“…The CDR3 composition of both IgM ϩ B cell subsets was comparable in length, number of N-nucleotides, exonuclease activity at the J H gene segment and the number of D-segments used. This is in contrast with data obtained from the mouse, in which CD5 ϩ B cells had limited N-nucleotides or exonuclease activity (46). This discrepancy most likely reflects differences in the generation of the CDR3 between mouse and man since data obtained from human cord blood CD5 ϩ and CD5 Ϫ B cells were very similar to results obtained in this study (17).…”

IgE Transcripts in the Circulation of Allergic Children Reflect a Classical Antigen-Driven B Cell Response and Not a Superantigen-Like Activation

“…Second, IgE sequences were found to contain a strikingly low level of somatic hypermutation and include significantly shorter CDR-3 (8). These characteristics have also been reported for transcripts from CD5 + B cells (10), which share similarities with murine B-1a cells (11) and arise from polyclonal activation (12). Therefore, it was hypothesized that B-1 cell activation might also play a role during allergic immune responses (8,13).…”

Human Hematopoietic Stem/Progenitor Cells Generate CD5+B Lymphoid Cells in NOD/SCID Mice

“…The development and the role of B lymphoid cells expressing the surface antigen CD5 (also called B-1a) are enigmatic [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64]. For example, it is not yet known whether CD5 + B cells derive from progenitors distinct from those which generate CD5 -B cells or if they instead represent an activated B-cell subset [53].…”

“…A further decrease in the numbers of CD5 + B cells is observed during late adulthood [76]; these cells are almost undetectable in human adult BM [61] and account for <5% of peripheral blood and peritoneal lymphocytes of humans older than 45 years [66]. Studies in the mouse suggest that CD5 + B cells are produced preferentially or exclusively early in the ontogeny and are still capable of self-replenishment in the adult [54,58].…”