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

• Published in: The Journal of immunology (1950) Vol. 149; no. 12; pp. 3817 - 3826
• Main Authors: Lederman, S, Yellin, MJ, Inghirami, G, Lee, JJ, Knowles, DM, Chess, L
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.12.1992; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Antigens, CD - immunology; Antigens, Differentiation, B-Lymphocyte - immunology; Antigens, Differentiation, T-Lymphocyte - immunology; Antigens, Surface - immunology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Biological and medical sciences; CD2 Antigens; CD4-Positive T-Lymphocytes - immunology; CD40 Antigens; Cell Adhesion Molecules - immunology; Cell Communication - immunology; Cell interactions; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation - immunology; Humans; Immunity, Cellular; Immunobiology; Intercellular Adhesion Molecule-1; Interleukin-2 - pharmacology; Interleukin-4 - pharmacology; Lymphocyte Activation - immunology; Lymphocyte Cooperation; Lymphocyte Function-Associated Antigen-1 - immunology; Lymphoid Tissue; Receptors, Complement 3d - immunology; Receptors, IgE - biosynthesis; Receptors, IgG - immunology; Receptors, Immunologic - immunology; Recombinant Proteins - pharmacology; Tumor Necrosis Factor Receptor Superfamily, Member 7; Human; Lymphoid cell; Cell contact; Follicular cell; T-Lymphocyte; Cell cell interaction; Molecular interaction; B-Lymphocyte; Lymphoid tissue; Cell surface
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.149.12.3817

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.