Ea. Reap et al., CONVENTIONAL B-CELLS, NOT B1 CELLS, ARE THE SOURCE OF AUTOANTIBODIES IN CHRONIC GRAFT-VERSUS-HOST DISEASE, The Journal of immunology, 151(12), 1993, pp. 7316-7323
B1 (CD5+) B cells have been implicated as a source of certain autoanti
bodies in several murine and human studies. We have previously shown i
n the lpr model of autoimmunity, however, that conventional B cells, n
ot B1 cells, were the source of autoantibodies directed at chromatin,
ssDNA, and IgG. In the current study, we have investigated the origin
of autoantibodies in chronic graft-versus-host (GVH) disease, induced
in nonautoimmune mice by transferring Ia-incompatible spleen cells. GV
H mice develop multiple autoantibodies and significant kidney damage.
Therefore, this model allowed us to examine the B cell subset involved
in both autoantibody production and tissue injury. We used two protoc
ols to establish B cell chimeras that possessed immunoglobulin heavy c
hain (Igh) allotype-marked peritoneal (B1-cell source) cells and bone
marrow-derived (conventional B cell source) cells from nonautoimmune C
57BL/6kh (B6) congenic mice. In both types of chimeras, chronic GVH wa
s induced by giving mice alloreactive T cells i.p. All of the subseque
nt anti-chromatin, RF, and anti-ssDNA autoantibodies were produced by
the conventional B cells and not by B1 cells. In addition, glomerular
immune complex deposits of both IgM and IgG originated from the conven
tional B cells and not from B1 cells. These findings thus parallel tho
se from our previous work on autoantibodies in lpr, and extend those f
indings by demonstrating that antibodies within pathogenic immune comp
lexes in the kidneys are also exclusively of conventional B cell origi
n.