Abstracts (complete list) - Wissenschaft Online

Bishnudeo Roy, Oliver Pabst, Swati Shukla, Sandra Düber, Siegfried Weiss
Contribution of B-1 cells to gut associated humoral immunity
The relative contribution and repertoire of B-1 and B-2 cell derived IgA in the gut
immune system is still a controversial issue. The lack of an exclusive B-1 cell marker
has made it difficult to delineate the B-1 and B-2 cell derived IgA producing plasma
cells. To circumvent these problems, we have used the L2 mouse line which is
transgenic for λ2315 light chain and virtually consists of B-1 cells exclusively. A
particular feature of these mice is the presence of a few B-1 cell derived specificities at
dominating frequencies in the peritoneum. In this work, these specificities, detectable
as VH sequences, were used as markers to investigate the participation of B-1 cells in
IgA production at the intestinal mucosa.
Analysis of IgM VH sequences derived from Peyer´s patches (PP) B cells of L2 mice
showed that 10% of these IgM VH sequences were identical to IgM VH sequences
derived from peritoneal cavity (PEC) B-1 cells of these mice. Also, some commonality
amongst the IgM VH sequences derived from the lamina propria (LP) B cells, and PEC B-
1 cell associated sequences from L2 mice could be observed.
On the other hand, analysis of IgA VH sequences derived from the LP and PP B cells
showed no match with B-1 cell associated Ig VH sequences. Additionally, IgA VH sequences derived from the LP associated plasma B cells was rather heterogeneous and
showed N/P nucleotide addition in the CDR3 region and somatic hypermutation through
out the VH chain. Histology done for the intestine showed a decreased number of IgA+
plasma cells in the LP of L2 mice in comparison to NT control mice. Consistent with this,
there was a decrease in the levels of secretory IgA in the intestinal lumen of L2 mice.
In addition, IgA expressing B cells, majority of which was B-1 cells (IgA+CD43+) could
be observed in the PEC of L2 as well as NT mice. Analysis of PEC B-1b cell derived IgA
VH sequences of normal mice showed the presence of nucleotide exchanges through out
the VH sequences at a high frequency.
Altogether, these data suggest that IgA producing B cells might be a highly selected
population and PEC B-1 cells might diversify due to antigen driven selection in the
GALT.