Interleukin 4 Induces the Maturation of Idiotype-Specific Regulatory B Cell Populations

Abstract

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 lgH^b-linked idiotypic determinants on anti-(4-hydroxy-3-nitrophenyl) acetyl (NP) antibody (Nb^b) 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 NP^b idiotype-specific cells panned on antibody-coated petri dishes or sorted by flow cytometry from spleen were capable of augmenting NP^b 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⁺, lgM⁺, 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.