title: The Ba fragment of complement factor B inhibits human B lymphocyte proliferation.
abstract: Normal human B lymphocyte function is finely regulated by both positive and negative signals at each stage of activation, proliferation, and differentiation. Activation signals include antigen and surface Ig cross-linking agents such as anti-mu or anti-delta. Signals inducing proliferation include IL-2, high m.w.-B cell growth factor (BCGF), and low m.w.-BCGF. IL-2 as well as IL-6 and other partially characterized B cell differentiation factors can induce terminal differentiation of proliferating B cells into Ig-secreting plasma cells. Various C components have been described to regulate B cell function including Bb that enhances proliferation, C5a that enhances Ig production, and C3a that inhibits Ig production. In our study, we examined the ability of the factor B cleavage fragment Ba to influence human B cell function. Ba did not affect the activation of resting B cells but inhibited the proliferation of activated B cells stimulated with either high m.w.-BCGF or low m.w.-BCGF. The inhibition occurred with doses of Ba as low as 1 microgram/ml (29 nM). Ba was found to bind to activated human B lymphocytes in a saturable manner with an apparent K of approximately 25 nM and an apparent Bmax of 56,000 sites/cell. A peptide made of the carboxy terminal 10 amino acids of Ba (GHGPGEQQKR), was also found to inhibit growth factor induced proliferation of activated B cells but at an ID50 of approximately 5 microM. Finally, Ba was found to inhibit the terminal differentiation of Staphylococcus aweus Cowan-activated B cells stimulated with B cell differentiation factors but not Ig secretion by the partially differentiated EBV-transformed cell line SKW.6. Thus, concentrations of Ba achievable in vivo at sites of active inflammation were found to act on human B lymphocytes by inhibiting their proliferation. This may act to limit the immune response to a specific antigenic challenge.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: J L
authors.initials: JL
authors.lastname: Ambrus
authors.forename: M G
authors.initials: MG
authors.lastname: Peters
authors.forename: A S
authors.initials: AS
authors.lastname: Fauci
authors.forename: E J
authors.initials: EJ
authors.lastname: Brown
mesh_terms: D000595:Amino Acid Sequence; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D011415:Complement Factor B / Q000494:pharmacology*; D004792:Enzyme Precursors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments
chemical_list: D004792:Enzyme Precursors; D009842:Oligopeptides; D010446:Peptide Fragments; D015847:Interleukin-4; D011415:Complement Factor B