Strong antigenic selection shaping the immunoglobulin heavy chain repertoire of B-1a lymphocytes in λ2315 transgenic mice

Abstract

The B lymphocyte compartment of the recombinant mouse line L2 consists predominantly of CD5+ B‐1 cells that exclusively express the transgenic (Tg) λ2 L chain of the plasmacytoma MOPC315. Using such Tg mice as a simplified model to study positive selection processes, we show that restriction to a single L chain results in a strongly oligoclonal IgH chain repertoire in fetal and neonatal liver‐derived B cells, as well as in peritoneal CD5+ B‐1 lymphocytes from adult mice. In contrast, in vitro differentiated fetal liver Pro/PreB‐I cells from L2 embryosshow a clear increase of complementarity determining region three (CDR3) diversity. These data suggest that the antibody repertoire of B‐1a cells is strongly selected by antigen during fetal as well as adult peritoneal phase.

B‐1‐cell subpopulations contribute differently to gut immunity

“…Among 29 of such sequences, two were found to be identical to already known B-1a-cell sequences from PEC of L2 mice (Table 1, Sort II). Again, one of these sequences (PP1.2) could be attributed to the sequence found most frequently amongst PEC B-1a-cell-derived IgMVH sequences of L2 mice [17]. All these sequences, which were found to be identical to PEC B-1a-derived sequences, lacked the presence of N/P nucleotides at the V-D/D-J junctions (Table 1), representing another characteristic of many B-1-cell-derived VH sequences.…”

“…If yes, then there should be some overlap between the repertoires of B-1 cells from these two compartments. To investigate the possible commonality, previously established PEC B-1a-cell (IgM + CD5 + )-associated IgVH sequences of L2 mice [17,18] were used as molecular markers to track the presence of such B cells in the PP of L2 mice.…”

“…In addition, some repertoire dominating sequences could be found repeatedly in different mice [17,18]. Thus, a substantial fraction of B-1a cells expresses identical BCRs on their surface providing an excellent molecular marker for such cells.…”

“…If yes, then there should be some overlap between the repertoires of B-1 cells from these two compartments. To investigate the possible commonality, previously established PEC B-1a-cell (IgM + CD5 + )-associated IgVH sequences of L2 mice [17,18] were used as molecular markers to track the presence of such B cells in the PP of L2 mice.Using this concept, IgMVH sequences derived from bulk sorted GC B cells (CD19 + PNA Hi/Int ) from PPs of L2 mice were analyzed. Of 43 such IgMVH sequences, four were found to be identical (100% CDR3 region nucleotide sequence match) to already known (a dataset of around 800 sequences) PEC B-1a-cell-derived IgMVH sequences of L2 mice (Table 1, Sort I).…”

“…Of 43 such IgMVH sequences, four were found to be identical (100% CDR3 region nucleotide sequence match) to already known (a dataset of around 800 sequences) PEC B-1a-cell-derived IgMVH sequences of L2 mice (Table 1, Sort I). One of these sequences (PP1) was among the dominantly found PEC B-1a-cell-derived IgMVH sequences [17]. In addition to IgMVH sequences derived from GC B cells, the IgMVH sequences derived from non-GC transgenic B cells (κ − IgM + PNA − ) from the PP of L2 mice were also examined independently.…”