EVIDENCE THAT INTESTINAL IGA PLASMA-CELLS IN MU,CHI TRANSGENIC MICE ARE DERIVED FROM B-1 (LY-1 B) CELLS

B6-Sp6 transgenic mice carry fully rearranged (BALB/c-derived. Igh-C(a ) allotype) mu heavy chain and kappa light chain transgenes, specific for trinitrophenyl, on a C57BL background (Igh-C(b) allotype). FACS an alyses show that the majority of B cells in peripheral lymphoid organs and bone marrow (BM) express transgenic IgM exclusively. A small prop ortion of the B cells, however, express endogenous IgM, usually concom itant with transgenic IgM. Three criteria establish that the endogenou s IgM expressing B cells belong to the B-1 cell lineage. (i) Endogenou s IgM expressing B cells in B6-Sp6 mice have the same localization pat tern as B-1 cells from normal animals: they are enriched in the perito neal cavity. (ii) The endogenous IgM+ B cells have the phenotype of B- 1 cells: the endogenous IgM+ peritoneal B cells express Mac-1 (CD11b) and low levels of IgD, and most also express CD5 (Ly-1). (iii) B6-Sp6 BM poorly reconstitutes endogenous IgM+ B cells, just as adult BM from normal mice poorly reconstitutes B-1 cells. In contrast, B cells whic h only express the transgene are readily reconstituted by B6-Sp6 BM. T he few endogenous IgM+ cells in the B6-Sp6 BM recipients are located i n the peritoneal cavity and have the phenotype of B-1b cells (previous ly the Ly-1 B sister population), which are known to be reconstituted by adult BM. Two-color immunofluorescence staining of tissue sections from the gut and from isolated gut lamina propria cells shows the pres ence of many IgA containing cells, about one-third of which simultaneo usly express cytoplasmic (transgenic) IgM. The C-region of this IgA is produced by endogenous C(alpha) genes, because the transgene encodes only for C(mu). Furthermore, the majority of gut IgA containing cells do not express the idiotype of the transgene, indicating that most of the gut IgA cells are encoded by endogenous V(H) genes and thus the re sult of an isotype switch from endogenous IgM expressing B cells. Sinc e the endogenous IgM+ cells are B-1 cells (both B-1a and B-1b), the da ta strongly indicate that the intestinal IgA plasma cells also belong to the B-1 cell lineage.