Mitogenic effect of alpha 1-microglobulin on mouse lymphocytes. Evidence of T- and B-cell cooperation, B-cell proliferation, and a low-affinity receptor on mononuclear cells.
Human alpha 1-m microglobulin (alpha 1-m), a low molecular weight plasma protein, was found to exert mitogenic effects on mouse lymphocytes from lymph nodes and spleen. The stimulatory effects appeared to be strain-restricted: alpha 1-m induced a varying degree of proliferation of lymphocytes from three strains, whereas one strain responded poorly. Experiments with lymphocyte subpopulations showed only weak stimulatory effects of alpha 1-m on purified T and B lymphocytes cultivated alone. The addition of mitomycin-treated cells of the other subpopulation could not restore the proliferative responses in either T or B lymphocytes. Strong stimulations were recorded only when both T and B lymphocytes were present, indicating that the T and B lymphocytes cooperate to achieve the proliferation. However, FACS studies on cultured splenocytes indicated that the proliferating cells are predominantly B lymphocytes. These data extend our earlier findings of a mitogenic effect of alpha 1-m on guinea pig lymphocytes. Furthermore, results were obtained indicating the presence of a receptor on mononuclear cells. Iodine-labelled alpha 1-m was bound to mononuclear cells prepared from spleens, and the binding could be blocked by an excess of non-labelled alpha 1-m. Scatchard plotting of the data gave an equilibrium constant of 0.7 x 10(5)/M for the binding between alpha 1-m and the receptor. Together with the documented inhibitory activity of alpha 1-m on antigen-driven proliferation of lymphocytes, these results suggest an immunoregulatory role for alpha 1-m.
Department of Physiological Chemistry, University of Lund, Sweden.
H
H
Babiker-Mohamed
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B
Akerström
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L
Lögdberg
D000510:Alpha-Globulins / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D007963:Leukocytes, Mononuclear / Q000032:analysis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D011971:Receptors, Immunologic / Q000032:analysis*; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D000510:Alpha-Globulins; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; C057015:alpha(1)-microglobulin receptor; C016001:alpha-1-microglobulin