Autoantibodies inhibit interleukin-7-mediated proliferation and are associated with the age-dependent loss of pre-B cells in autoimmune New Zealand Black Mice.
Surface IgM+B220+ B cell precursors can be categorized as either leukosialin (CD43/S7) negative (late stage pre-B cells) or positive (pro-B/early pre-B cells). In autoimmune New Zealand Black (NZB) mice, bone marrow small pre-B cells (IgM-CD43-B220+) and pro-B/early pre-B cells (IgM-CD43+B220+) declined significantly with age. In particular, subpopulations of pro-B/early pre-B cells expressing the heat stable antigen (HSA) were found in lower proportions with age. Significant decreases in interleukin-7 (IL-7) colony forming units (CFU) were also seen in NZB mice by 6 to 8 months of age and accompanied alterations in the numbers of pro-B and pre-B cells in bone marrow. Concomitant with reduced numbers of B lineage precursor cells and IL-7 CFU in vivo, NZB mice produced serum IgM antibodies that strongly inhibited IL-7 CFU responses in vitro. Two monoclonal IgM antibodies (5G9, 2F5) derived from LPS stimulated 10-month-old NZB splenocytes recognized pre-B cell surface antigens on both pre-B cell lines and on IL-7 stimulated bone marrow pro-B/pre-B cells. However, these monoclonal antibodies (MoAb) failed to significantly stain ex vivo bone marrow cells. The 5G9 and 2F5 MoAbs also partially inhibited IL-7 CFU in vitro. These results suggest that NZB bone marrow becomes increasingly deficient in B cell precursors and especially in IL-7 responsive pre-B cells with age. IgM serum antibodies and monoclonal IgM antibodies derived from older NZB mice inhibit pre-B cell growth to IL-7. The production of such autoantibodies may interfere with B cell development in aging NZB mice by preventing IL-7-mediated proliferation.
Merchant
M S
MS
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101, USA.
Garvy
B A
BA
Riley
R L
RL
D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology; D015703:Antigens, CD; D001323:Autoantibodies / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology*; D001402:B-Lymphocytes / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D016923:Cell Death; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D007075:Immunoglobulin M / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D015851:Interleukin-7 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051917:Leukosialin; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB / Q000276:immunology*; D012795:Sialoglycoproteins / Q000032:analysis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001323:Autoantibodies; D007075:Immunoglobulin M; D015851:Interleukin-7; D051917:Leukosialin; D012795:Sialoglycoproteins; C497863:Spn protein, mouse