Fgm. Kroese et al., EVIDENCE THAT INTESTINAL IGA PLASMA-CELLS IN MU,CHI TRANSGENIC MICE ARE DERIVED FROM B-1 (LY-1 B) CELLS, International immunology, 5(10), 1993, pp. 1317-1327
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.