Surface immunoglobulin ligands and cytokines differentially affect proliferation and antibody production by human CD5+ and CD5- B lymphocytes.
Normal human peripheral blood B lymphocytes were separated into CD19+ CD5+ and CD19+ CD5- subsets by dual-color FACS sorting. In most experiments the cells were activated with Staphylococcus aureus Cowan I (SAC) and cultured in the absence or presence of recombinant human IL-1 alpha, IL-2, or IL-6, or combinations of these cytokines. Unstimulated CD5+ and CD5- B cells showed a comparable, low level of incorporation of [3H]thymidine into DNA. SAC stimulated proliferation of CD5+ and CD5- B cells, and this proliferation was augmented by IL-2 in the case of CD5- B cells. Anti-mu beads stimulated some proliferation of the CD5- subset and augmented SAC-induced proliferation of these cells. In contrast, anti-mu beads did not stimulate proliferation of the CD5+ subset and had no effect on SAC-induced proliferation of these cells. CD5+ B cells activated by anti-mu beads were stimulated to proliferate in the presence of IL-4, but not in the presence of IL-2. These observations support the interpretation that two signals are required for proliferation of CD5+ B cells. Using a two-step culture system, SAC activation itself did not induce Ig production by either subset of purified B cells. However, it primed the cells for antibody production in the presence of IL-2. IL-1 and IL-6 by themselves augmented antibody formation by these cells slightly, if at all. However, IL-6, and to a lesser extent IL-1, augmented antibody production in the presence of IL-2. Under the culture conditions used CD5- B cells produced IgM, IgG, and IgA whereas the CD5+ B cells produced almost exclusively IgM. The expression on B cells of surface activation markers was analyzed after culture for 2 days with SAC or anti-mu beads. In both subsets expression of Leu-23 and Leu-21 was increased, with some differences in intensity (Leu-23 greater in CD5+ cells, Leu-21 greater in CD5- cells). SAC increased IL-2R expression to a greater extent than anti-mu beads. In neither subset was expression of CD23 increased. These observations are discussed in the context of the possible role of the CD5+ subset of B lymphocytes as components of a system of natural immunity.
Nawata
Y
Y
Department of Immunology, Syntex Research, Palo Alto, CA 94304.
Stall
A M
AM
Herzenberg
L A
LA
Eugui
E M
EM
Allison
A C
AC
D000888:Antibodies, Anti-Idiotypic; D000917:Antibody Formation; D000943:Antigens, Differentiation; D000944:Antigens, Differentiation, B-Lymphocyte; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D018956:CD5 Antigens; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D007148:Immunoglobulin mu-Chains; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D011947:Receptors, Antigen, B-Cell; D013211:Staphylococcus aureus / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000943:Antigens, Differentiation; D000944:Antigens, Differentiation, B-Lymphocyte; D018956:CD5 Antigens; D016207:Cytokines; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell