title: Interleukin 4 induces the maturation of idiotype-specific regulatory B cell populations.
abstract: CD5+ B cells have been shown to be disproportionately associated with autoimmune diseases and transformation. In many cases, their apparent ability to bypass self-tolerance is manifested by the production of autoantibodies. These observations, plus the hypothesis that CD5+ B cells represent a distinct B cell lineage, encourage studies into the conditions and factors that influence their development. In the present study, we employed a well-established assay for murine CD5+ B cell function, i.e., their ability to augment the responses of IgHb-linked idiotypic determinants on anti-(4-hydroxy-3-nitrophenyl) acetyl (NP) antibody (Nbb) idiotype-bearing CD5- B cells to a T-independent antigen, together with multiple methods of cell surface phenotyping, to evaluate the potential for interleukin (IL) 4 to effect maturation of CD5+ B cells, CD5+, IgM+, Thy-1-, and NPb idiotype-specific cells panned on antibody-coated petri dishes or sorted by flow cytometry from spleen were capable of augmenting NPb idiotypic responses of NP-KLH-primed responder cells to NP-Ficoll. Splenic B cell populations depleted of CD5+ B cells failed to affect idiotype expression even after 2 days in culture, a time when a small percentage of CD5+ B cells appeared to be regenerated. However, idiotype-specific regulatory activity could be restored in CD5- splenic B cell populations by culture for 2 days with recombinant IL-4. Cells responsible for idiotype-specific regulatory activity after culture with IL-4 were in fact CD5+, IgM+, and Thy-1.2- B cells, demonstrating that IL-4 can drive the functional, if not the phenotypic, maturation of splenic B cells associated with the CD5+ B cell lineage. The results illustrate one possible mechanism by which T cells could control the maturation of cells belonging to the CD5+ B cell lineage.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: J A
authors.initials: JA
authors.lastname: Hardin
authors.forename: M
authors.initials: M
authors.lastname: Gibson
authors.forename: E
authors.initials: E
authors.lastname: Grant
authors.forename: D H
authors.initials: DH
authors.lastname: Sherr
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009596:Nitrophenols / Q000276:immunology; D010648:Phenylacetates; D013154:Spleen / Q000166:cytology
chemical_list: D015703:Antigens, CD; D018956:CD5 Antigens; D000939:Epitopes; D007130:Immunoglobulin Idiotypes; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid; D015847:Interleukin-4