title: The molecular interactions with helper T cells which limit antigen-specific B cell differentiation.
abstract: Helper T (Th) cell-dependent activation requirements for 2,4,6-trinitrophenyl (TNP)-specific resting B cells obtained from mice transgenic for Sp-6 mu, kappa genes were analyzed. Carrier-specific T cell help required linked recognition of TNP carrier and was functionally restricted by the B cell major histocompatibility complex. However, histoincompatible T cell-B cell conjugates formed by bridging surface immunoglobulin and Th cell receptor for antigen (TcR) through TNP-conjugated anti-TcR antibodies resulted in the efficient differentiation of TNP-specific B cells. Thus, Th cell-dependent cognate recognition of B cells is not obligatory. Specific conjugate formation could be obviated by using unconjugated fragments of anti-TcR antibodies. If dimeric, these fragments supported the Th cell-dependent differentiation of co-cultured histoincompatible resting B cells. Unconjugated monomeric fragments were ineffective, demonstrating the necessity for TcR cross-linking. Resting B cells from Sp-6+ mice rendered TNP-conjugated monomeric fragments of anti-TcR antibodies effectively multivalent, thereby satisfying conditions for the activation of co-cultured Th cells. The results demonstrate that Th cells do not transduce activation signals through TcR recognition of B cell membrane-associated ligand which limit the induction of B cell differentiation. Cross-linking of TcR on Th cells is required, sufficient and can be induced through interaction with the antigen-specific B cell surface.
authors.affiliation: Department of Immunology, McGill University, Montreal, Quebec, Canada.
authors.forename: M H
authors.initials: MH
authors.lastname: Julius
authors.forename: H G
authors.initials: HG
authors.lastname: Rammensee
authors.forename: M J
authors.initials: MJ
authors.lastname: Ratcliffe
authors.forename: M C
authors.initials: MC
authors.lastname: Lamers
authors.forename: J
authors.initials: J
authors.lastname: Langhorne
authors.forename: G
authors.initials: G
authors.lastname: Köhler
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins