Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles. Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help.
In lymphoid follicles, CD4+ T lymphocytes provide contact-dependent stimuli to B cells that are critical for the generation of specific antibody responses in a process termed Th function. The CD4+ T cell-restricted surface activation protein, 5c8 Ag (T-BAM), has recently been shown to be a component of the contact-dependent helper signal to B cells. To further dissect this process, we utilized a Jurkat T cell lymphoma clone, termed D1.1, that constitutively expresses T-BAM and activates peripheral B cells to express surface CD23 in a contact-dependent mechanism that is inhibited by mAb anti-T-BAM (5c8). Similar to its effect on peripheral B cells, Jurkat D1.1 activates B cells from lymphoid organs, as well as a B cell lymphoma clone, RAMOS 266,4CN 3F10 (RAMOS 266), to up-regulate surface CD23. Interestingly, mAb to the B cell surface molecule, CD40 (mAb G28-5 and B-B20), inhibit D1.1 induced activation of RAMOS 266 and peripheral and lymphoid B cells. In contrast, mAb to CR2 or the adhesion molecules, LFA1, LFA3, or ICAM-1, have little effect. The inhibitory effect of anti-CD40 mAb on B cell activation induced by D1.1 is specific because anti-CD40 potentiates, rather than inhibits, the up-regulation of CD23 on B cells induced by rIL-4. Moreover, cross-linking CD40 molecules by anti-CD40 mAb bound to Fc gamma RII+ (CD32) L cells induces B cell CD23 expression. In vivo, T-BAM-expressing cells are CD4+ T cells that are restricted to lymphoid organs and are localized in the mantle and centrocytic zones of lymphoid follicles and the spleen periarteriolar lymphoid sheath in association with CD40+ B cells. Taken together, these data demonstrate that T-BAM on T cells and CD40 on B cells are involved in contact-dependent T-B help interactions that occur in lymphoid follicles.
D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018801:CD2 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D018799:Intercellular Adhesion Molecule-1; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008211:Lymphocyte Cooperation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008221:Lymphoid Tissue; D017464:Receptors, Complement 3d / Q000276:immunology; D017455:Receptors, IgE / Q000096:biosynthesis; D017452:Receptors, IgG / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4