Proliferation and differentiation of human CD5+ and CD5- B cell subsets activated through their antigen receptors or CD40 antigens.
The pan-T cell antigen CD5 has been shown to delineate two different mouse B cell subsets, originating from distinct progenitors. In man, on average, 30% of the tonsillar B cell pool expresses this antigen. In the present report, a detailed comparison of the CD5+ and CD5- B cell response to cytokines, following activation via surface immunoglobulins (sIg) or CD40 antigen, was undertaken. CD5+ B cells were positively selected by panning or by sorting from tonsils. Two-color immunofluorescence analysis performed on tonsillar B cell populations showed that CD5+ B cells displayed most of the phenotypic features of mantle zone B cells. CD5+ B cells could be stimulated for DNA synthesis by mitogenic concentrations of Staphylococcus aureus, Cowan I strain (SAC), insolubilized anti-IgM antibodies, immobilized anti-CD40 antibodies and phorbol 12-myristate 13-acetate (PMA). The growth-response of small dense CD5- B cells to these T cell-independent mitogens was comparable to that of CD5+ B cells, whereas the low-density, in vivo-activated, CD5- B cells were only marginally stimulated by Ig-cross-linking agents and PMA. Following ligation of sIg, both B cell subsets proliferated essentially in response to interleukin (IL)-2 and IL-4. When used in co-stimulation with immobilized anti-CD40 antibodies, IL-4 promoted growth of CD5+ and CD5- B cells, whereas IL-2 displayed only moderate stimulatory effects. CD5+ and CD5- B cells differentiated into Ig-secreting cells when they were co-cultured with SAC or cross-linked anti-CD40 antibodies and IL-2. However, IgM constituted the major component of the Ig response of CD5+ B cells, whereas high levels of IgG were secreted by CD5- B cells.
Defrance
T
T
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Vanbervliet
B
B
Durand
I
I
Briolay
J
J
Banchereau
J
J
D015703:Antigens, CD / Q000032:analysis* / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D019013:CD40 Antigens; D018956:CD5 Antigens; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D008213:Lymphocyte Activation; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D018956:CD5 Antigens; D016207:Cytokines; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell