Expansion of CD22lo B cells in the spleen of autoimmune-prone flaky skin mice.
Similar to murine models with compromised CD22/SHP-1 function, flaky skin (fsn) mutant mice exhibit lymphocyte hyperactivation and an autoimmune phenotype characterized by circulating autoantibodies to dsDNA and glomerulonephritis. Immunophenotyping of fsn/fsn splenic B cells was performed to determine if abnormalities in CD22 expression contributed to the phenotype. We identified an expansion of an IgM(bright) CD22lo population consistent with immature B-lymphocytes. While normal B-lymphocytes require IL-4 to achieve down-modulation of CD22 expression in response to BCR cross-linking, culture with anti-IgM alone led to reduced CD22 expression in fsn/fsn mice. Furthermore, when IL-4 was added to fsn/fsn cultures, no further reduction in CD22 expression was observed. This suggested that fsn/fsn B cells were pre-activated in vivo by chronic IL-4 exposure. A portion of these CD22lo cells expressed the B-1 surface marker CD11b. We contend that decreased activation thresholds among CD22lo B-lymphocytes contributes to the expansion of immature and B-1 B cell populations and to the development of autoimmune pathology in fsn/fsn mice.
Mattsson
Nancy
N
Department of Applied Medical Sciences and Bioscience Research Institute of Southern Maine, University of Southern Maine, Portland, ME 04103, USA.
Duzevik
Eliza Grlickova
EG
Pelsue
Stephen C
SC
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D007075:Immunoglobulin M / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D037102:Lectins / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D051918:Sialic Acid Binding Ig-like Lectin 2; D012868:Skin Abnormalities / Q000276:immunology*; D013154:Spleen / Q000166:cytology* / Q000276:immunology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D007075:Immunoglobulin M; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D015847:Interleukin-4