Contribution of B-1 Cells to Intestinal IgA Production in the Mouse

Abstract

In this paper we review the existing evidence that peritoneally derived B-1 cells may contribute significantly to the generation of IgA-secreting plasma cells in the murine intestinal lamina propria. The evidence is based upon a variety of experimental approaches performed in our laboratory and others and include (i) transfer studies of (sorted) B-1 cells into B-cell-depleted mice either experimentally (X-irradiation, anti-μ treatment) or genetically (SCID), (ii) analysis of genetically modified or manipulated mice (motheaten mice, CBA/N Xid mice, μ,k transgenic mice), and (iii) transplantation studies of fetal omentum. The data thus support the view that in addition to conventional B cells (B-2 cells) located in the Peyer′s patches (PP), B-1 cells contribute to the pool of IgA containing cells in the gut. Indeed, cotransfer of PP cells and peritoneal cells (PerC), which contain largely B-1 cells, into SCID recipients demonstrates that both PP and PerC contribute in a balanced fashion to the pool of IgA-containing cells in the gut lamina propria over long periods. Most likely IgA-positive (memory) B cells in PP are responsible for the long-term generation of IgA-producing cells derived from the PP inoculum. The potency of B-1 cells to contribute to mucosal IgA responses is also illustrated in adoptive transfer experiments in which PerC B-1 cells (or sorted B-1 cells) are adoptively transferred into untreated, Ig allotype congenic, SCID mice. These studies show that 6 months after injection of a few million PerC, almost all B cells in spleen and the recipient′s peritoneal cavity have the B-1 cell phenotype, while approximately 40 million PerC donor-derived IgA-producing cells can be detected in the gut lamina propria by allotype-specific ELISA spot assays. In conclusion, the data presented here show that, in principle, B-1 cells located in the peritoneal cavity may be an important source of precursors for intestinal IgA plasma cells in the mouse. However, the experiments performed so far do not allow us to draw definitive conclusions yet on the physiological contribution (in terms of numbers) and function (in terms of their specificity repertoire) of both B-1 cells and Peyer′s patch-derived B-2 cells to the pool of IgA-containing cells in the gut lamina propria in normal, unmanipulated animals.