In vitro tolerance induction of neonatal murine B cells.

Abstract

Immunologic tolerance was originally defined as specific hyporesponsiveness to an antigen which results from prior contact with that antigen (1, 2). The concept of natural tolerance to self-antigens was perceived by Burnet (3) as the deletion of clones reactive to autologous antigens after contact of these antigens with the reactive cells' specific antigen receptors during the development of the cell's immunologic competence. If such a theory were to have physiological relevance, then several predictions should be realized: (a) developing cells should be significantly more susceptible to tolerance induction than their mature counterparts; (b) tolerance should be inducible over a wide range of antigen concentrations, since the concentrations of different self-antigens present presumably vary; (c) since the spectrum of self-antigens is diverse, the development of unresponsiveness should be plausible with a wide variety of antigenic structures; (d) since bone marrow-derived precursors to antibody-forming cells (B cells) presumably mature independently of other cell types, induction of B-cell tolerance should occur in the absence of antigen-specific thymus-derived lymphocytes (T cells); (e) the discrimination between self and nonself would be absolute, and therefore, tolerance should exhibit exquisite determinant specificity.

IL-4 Promotes Stat6-Dependent Survival of Autoreactive B Cells In Vivo Without Inducing Autoantibody Production

“…B cell tolerance that is induced by exposure to Ag in the absence of additional stimuli protects against the development of humoral autoimmunity (1)(2)(3). The characteristics of Ag-induced tolerance depend on the extent of B cell membrane Ig (mIg) 3 cross-linking by Ag.…”

Susceptibility to in vitro tolerance induction of adult B cells from mice with an X-linked B-cell defect.

“…The modification of the in vitro splenic focus assay for tolerance susceptibility has been described previously (12,13). Briefly, 4-6 × 106 viable spleen cells from (CBA/N × DBA/2)F1 females or males were injected intravenously into Hy-primed, irradiated, adult F1 female recipients.…”

“…Chicken (ovalbumin [OVA], Fraction V, Pentex Biochemical, Inc., Kankakee, Ill.) was used without further purification. The preparation of dinitrophenylated Hy (DNP-Hy), trinitrophenylated (TNP) Hy (TNP-Hy), DNP-mouse gamma globulin (DNP-M'tG), and TNP-OVA was described previously (12).…”

“…This conclusion is based primarily on the following observations. (a) 2,4-dinitrophenyl (DNP)-and PC-reactive splenic B cells are tolerizable only for the first few days after their initial expression in the murine neonate (12,13). (b) Neonatal bone marrow B cells can be rendered unresponsive to antigen longer in development than neonatal splenic B cells (13,14).…”

“…Previous studies, which used a modification of the in vitro splenic focus technique (12), have suggested that susceptibility to in vitro tolerance induction m a y serve as a functional marker for developing (immature) B cells and B-cell m a t u r a t i o n (12)(13)(14). This conclusion is based primarily on the following observations.…”