Y. Jiang et al., MAPPING OF A GENE FOR THE INCREASED SUSCEPTIBILITY OF B1 CELLS TO MOTT CELL-FORMATION IN MURINE AUTOIMMUNE-DISEASE, The Journal of immunology, 158(2), 1997, pp. 992-997
Mott cells, a pathologic state of plasma cells containing intracellula
r inclusions of Igs (Russell bodies), are frequent in lymphoid tissues
of murine and human autoimmune diseases. However, neither the genesis
nor the significance of Mott cells in autoimmune diseases is well und
erstood. We found that B1, but not B2, cells were induced in vitro to
form Mott cells in the presence of LPS or IL-5, but not other stimulan
ts, in a much higher frequency in autoimmune New Zealand Black (NZB) a
nd NZB x New Zealand White (NZB/W) F1 than in non-autoimmune disease-p
rone mice and notably athymic nude NZB/W F1 mice. Cell surface phenoty
pes of Mott cells were B220(+) CD5(+)CD43(+)CD11b(dull), while those o
f peritoneal macrophages were B220(-)CD5(-)CD43(dull)CD11b(+). We mapp
ed a locus (provisionally designated Mott-1) controlling Mott cell for
mation that was tightly linked to microsatellite marker loci, D4 Mit70
and D4 Mit48, of autoimmune NZB mice, which is in close proximity to
our recently mapped locus Imh-1 for hypergammaglobulinemia. This regio
n contains candidate genes that may be relevant to the aberrant B cell
activation and differentiation. We suggest that while the Mott cell b
y itself is not the effector for autoimmune disease, the genetically d
etermined aberrant maturational process of B1 cells that underlies the
pathogenesis of autoimmune disease forms the basis for Mott cell form
ation in a T cell-dependent manner.