Mapping of a gene for the increased susceptibility of B1 cells to Mott cell formation in murine autoimmune disease.
Mott cells, a pathologic state of plasma cells containing intracellular 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 understood. 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 stimulants, in a much higher frequency in autoimmune New Zealand Black (NZB) and NZB x New Zealand White (NZB/W) F1 than in non-autoimmune disease-prone mice and notably athymic nude NZB/W F1 mice. Cell surface phenotypes of Mott cells were B220+ CD5+ CD43+ CD11b(dull), while those of peritoneal macrophages were B220- CD5- CD43(dull) CD11b+. We mapped a locus (provisionally designated Mott-1) controlling Mott cell formation 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 region contains candidate genes that may be relevant to the aberrant B cell activation and differentiation. We suggest that while the Mott cell by itself is not the effector for autoimmune disease, the genetically determined aberrant maturational process of B1 cells that underlies the pathogenesis of autoimmune disease forms the basis for Mott cell formation in a T cell-dependent manner.
Jiang
Y
Y
Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Hirose
S
S
Hamano
Y
Y
Kodera
S
S
Tsurui
H
H
Abe
M
M
Terashima
K
K
Ishikawa
S
S
Shirai
T
T
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002874:Chromosome Mapping; D004198:Disease Susceptibility; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology*