T cell‐produced immunoglobulin binding factor (IBF) bears determinants coded for by the I region of the major histocompatibility complex and lacks allogeneic restriction

Abstract

An immunoglobulin binding factor (IBF) produced by in vivo alloantigen-activated T cells suppresses in vitro antibody production to sheep red blood cells (SRBC) and probably represents the soluble form of the T cell Fc receptor. To study the relationship between IBF and the major histocompatibility complex (MHC), two types of experiments were undertaken. First, different IBF were prepared by injecting thymocytes from mice of H-2k, H-2b and H-2d haplotypes into irradiated, allogeneic recipient mice. Cells recovered in the spleens five days later were incubated for 2 h at 37 degrees C, and IBF was purified by affinity chromatography on insolubilized IgG. Purified IBF was then applied to immunosorbents prepared with anti-H-2 and anti-Ia anti sera. Acid eluates were then tested for their suppressive activity on in vitro antibody production to SRBC. Under these conditions, IBF was found to react with antisera raised against products of the whole MHC and of the I region of the MHC, but not with anti-H-2 D antisera. These data indicate that IBF bears, or is associated with Ia determinants. Second, IBF preparations from mice of H-2k, H-2b, H-2d haplotypes were tested for their capacity to suppress the in vitro antibody production to SRBC by spleen cells of a series of mouse strains. The data indicate that IBF is not genetically restricted in its function.

Suppression of mitogen‐induced peripheral B cell differentiation by soluble Fcγ receptors released from lymphocytes

“…The effects observed with FcyR in cultures of human PBL are quite similar to those of murine IBF which suppresses primary antibody response and polyclonal activation by lipopolysaccharide without affecting the proliferative response [13], and mouse IBF itself was recently reported to inhibit the late stages of maturation of human B cells in the presence of P W or NOC extracts [14]. Alike those of IBF [15], the suppressive effects of human soluble FcyR are not restricted to syngeneic B cells.…”

Potentiating and suppressive IgE-binding factors are expressed by a single cloned gene.

“…Suemura et al (23) reported that an IgE-specific suppressive factor ("IgE-TsF") was absorbed by an alloantiserum specific for determinants of the (KABJE)d region (23). IgG-BF derived from H-2k and H-2d mouse T cells and an H-2k T-cell hybridoma were absorbed by anti-Ia antisera specific for the appropriate la haplotype (24,25). However, the 8.3 IgE-BF sequence shares no homology with class II gene products (10), and genes encoding rodent IgE-BF are members of a multigene family that is not related to genes of the major histocompatibility complex (12).…”

Construction of T cell hybridomas secreting allogeneic effect factor.

“…In addition to the results presented here, studies currently being conducted in collaboration with W. H. Fridman and colleagues have shown that both hybridomas 27 and 34 express Fc receptors (FcR) specific for immunoglobulins of the IgG class (FcRy) (W. H. Fridman, et al Manuscript in preparation.). Moreover, like a T cell hybridoma constructed by these same investigators that is also FcRy positive (33), both hybridoma 27 and 34 secrete immunoglobulin-binding factor (IBF) activity (35)(36)(37), and their line (designated T2D4) appears to secrete AEF-like enhancing activity. It should be emphasized, however, that preferential expression of either AEF-enhancing or IBF-suppressive activities by the T2D4 and our hybridoma lines depends critically on the culture conditions used for the preparation of the biologically active supernates.…”