title: T cell development in B cell deficient mice. III. Restriction specificity of suppressor T cell factor(s) produced in mice treated chronically with rabbit anti-mouse mu chain antibody.
abstract: A role for Igh linked genes and the idiotypes they encode has been implicated in the activity of a variety of T cell subpopulations. Idiotype restricted T cell function has been observed for helper and suppressor cell populations. The finding that T cell receptor genes are distinct from B cell receptor (Igh) genes strongly argues against a direct role for immunoglobulin genes in the determination of the T cell repertoire. Nevertheless, idiotypic Ig determinants may play an indirect role in influencing the ultimate composition of the T cell repertoire. One approach to this question involves evaluation of T cell activity upon development in an immunoglobulin deficient environment. The availability of antigens which elicit T cell and antibody responses characterized by the expression of dominant crossreactive idiotypes under the control of Igh genes provides an ideal approach to investigate the basis for the expression of Igh-like structures on T cells and the concomitant functional genetic restrictions they determine. Thus, we have prepared B cell deficient mice by continuous treatment, beginning at birth, with rabbit anti-mouse IgM. The network which comprises the suppressor T cell response to azobenzenearsonate (ABA) was then examined in normal and anti-mu treated mice to assess what role, if any, immunoglobulin encoded determinants play in influencing the composition of the peripheral T cell pool. The results clearly demonstrate that the absence of Ig+ B cells leads to major alterations in the composition of the T cell repertoire. Anti-mu treated, but not normal rabbit Ig treated, mice produce TsF1 which fails to suppress cytotoxic T lymphocyte or helper T cell responses of normal syngeneic mice, yet efficiently suppresses those of syngeneic anti-mu treated recipients. Reciprocally, normal TsF1, though suppressive in normal Igh-1 syngeneic recipients, fails to affect the development of responses in anti-mu treated syngeneic mice. TsF1 obtained from anti-mu treated mice is antigen-specific. Testing of anti-mu TsF in a variety of normal or anti-mu treated recipients reveals no MHC restrictions. In marked contrast, anti-mu TsF reflects a novel pattern of Igh functional restrictions. The observed Igh restrictions were found to map to the idiotype encoding VH regions of the Ig heavy chain gene cluster (Igh-VH). The results demonstrate that T cell maturation in the virtual absence of environmental immunoglobulin can lead to profound changes in the composition of the T cell compartment. The means by which the absence of Ig encoded determinants leads to such changes is speculated upon.
authors.affiliation: Harvard Medical School, Department of Pathology, Boston, MA 02115.
authors.forename: K T
authors.initials: KT
authors.lastname: HayGlass
authors.forename: S J
authors.initials: SJ
authors.lastname: Naides
authors.forename: B
authors.initials: B
authors.lastname: Benacerraf
authors.forename: M S
authors.initials: MS
authors.lastname: Sy
mesh_terms: D000361:Agammaglobulinemia / Q000276:immunology / Q000473:pathology*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000145:classification / Q000473:pathology*; D002454:Cell Differentiation; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D007970:Leukopenia / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D011817:Rabbits; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D011948:Receptors, Antigen, T-Cell; D013491:Suppressor Factors, Immunologic; C044203:anti-IgM