B cell growth and differentiation factors interact with receptors distinct from the interleukin 2 receptor.
Human B lymphocytes preactivated with Staphylococcus aureus Cowan strain I can proliferate and differentiate to Ig-secreting cells when cultured in the presence of recombinant interleukin 2 (IL2). We have compared 2 different B cell growth factors (BCGF) and a B cell differentiation factor (BCDF) to IL2 in the regulation of human B lymphocyte growth and differentiation. Utilizing a competitive binding assay, neither a high molecular weight BCGF (HMW-BCGF) nor a low molecular weight BCGF (LMW-BCGF) competitively inhibited the binding of radiolabeled IL2. Blocking studies with the anti-Tac monoclonal antibody demonstrated that B cell proliferation to IL2 was inhibited while a crude supernatant containing BCGF and IL2 was only partially inhibited. B cell Ig secretion induced by IL2 was also inhibited by anti-Tac while a crude supernatant and partially purified BCDF were not. Furthermore, IL2 plus BCGF was shown to enhance B cell proliferation better than either factor alone and IL2 plus a BCDF enhanced B cell Ig secretion better than either factor alone. By separating activated B cells into Tac-positive and Tac-negative fractions, much of the previously noted enhancement with the 2 factors was found to be secondary to the differential sensitivity of the 2 populations to BCGF and IL2 or BCDF and IL2. Thus, LMW-BCGF, HMW-BCGF and a partially purified BCDF appear to interact with receptors distinct from the IL2 receptor in mediating their effects on B cell growth and differentiation.
D000293:Adolescent; D000328:Adult; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001667:Binding, Competitive; D002454:Cell Differentiation / Q000187:drug effects; D002648:Child; D004347:Drug Interactions; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology*; D008970:Molecular Weight; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000502:physiology; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; C048843:B-cell differentiation factor receptor; D006133:Growth Substances; D007376:Interleukin-2; D008222:Lymphokines; D011947:Receptors, Antigen, B-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D011994:Recombinant Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D015847:Interleukin-4