Helper T cell-dependent human B cell differentiation mediated by a mycoplasmal superantigen bridge.

Abstract

mAbs recognizing TCR V gene products have helped to define a unique group of potent T cell activators termed superantigens (1). Recognized superantigens include murine selfantigens (2, 3) and a group ofmicrobial toxins, the staphylococcal enterotoxins (SE) (1), and a soluble product ofMycoplasma arthritidis mitogen (MAM) (4). Superantigens share a number of intriguing characteristics. For example, superantigen recognition is almost entirely a function of TCR V a gene usage (1, 2).In addition, superantigens bind selectively and with high affinity to MHC class II molecules (6). In the absence of antigen processing and in an MHC-nonrestricted manner, superantigen-MHC class II complexes on the APC surface trigger the proliferation of T cells expressing the relevant TCR V gene product (5). Finally, the microbial toxins that function as superantigens are among the most potent mitogens known.The dual affinity of superantigens for MHC class II and TCR V gene products suggests that this class of antigen could promote a form of abnormal Th-B cell collaboration analogous to that observed during graft-vs .-host disease (GVHD). In GVHD, adoptive transfer of donor Th cells, specific for recipient MHC class II antigens, triggers polyclonal B cell activation . In selected strains of nonautoimmune prone mice, GVHD is characterized by an autoimmune diathesis remarkably similar to SLE (6). It has been suggested that in GVHD, the presence of both self antigens and donor-derived Th cells, reactive against recipient MHC class II antigens, provides a combination of stimuli that selectively drives autoreactive B cell differentiation (6).The experiments described below were designed to determine if a superantigen bridge between Th cells and B cells would result in an analogous form ofpolyclonal human B cell activation . MAM was selected for study in view ofthe chronic inflammatory arthritis that M. arthritidis induces in rodents (7), and scattered reports of M. arthritidis cultured from the bone marrow of patients with SLE (8).

MHC-Restricted Ig V Region-Driven T-B Lymphocyte Collaboration: B Cell Receptor Ligation Facilitates Switch to IgG Production

“…Nonlinked Id-driven B cell autoimmunity resembles the T celldriven autoimmune B cell responses observed with presentation of MHC alloantigens (46,47), viruses (48), superantigens (19,49), or B cells pulsed with synthetic peptide (50,51). In these cases, T-B collaboration is nonlinked in the sense that the B and T cell epitopes do not derive from the same Ag.…”

c-Rel is essential for B lymphocyte survival and cell cycle progression

“…We co-cultured purified B cells with + -irradiated SEB-reactive CD4 T helper cells in the presence or absence of superantigen. This superantigen-facilitated cognate T-B interaction represents a potent and physiological stimulus [25,26]. We found that stimulation of c-Rel(−/−) B cells with SEB-reactive Th cells in the presence of SEB resulted in a response that was only 25 % of that of the wildtype (Fig.…”

A potential role for microbial superantigens in the pathogenesis of systemic autoimmune disease

“…T cell line cells derived from 2 normal donors were used. After 10 days, cultures were terminated and supernatants were assayed for total IgM production by enzyme-linked immunosorbent assay, as described previously (60).…”