T helper cells recognize processed antigen (Ag) in the context of major histocompatibility complex (MHC) class II antigens present on the surface of B cells and other Ag‐presenting cells. This interaction is mediated through the T cell receptor complex with associate recognition of class II molecules by the CD4 molecule. In this study, the binding of a soluble recombinant CD4/Ig heavy chain fusion protein (CD4‐γ3) or monoclonal antibody (mAb) to class II antigens on human B cells was shown to induce rapid and specific homotypic adhesion of B cells and most B lymphoblastoid cell lines. mAb reactive with CD4 inhibited CD4‐γ3‐induced adhesion and a mutant B lymphoblastoid cell line deficient in class II antigens failed to respond. Induction of homotypic adhesion was dependent on energy metabolism and a functional cytoskeleton, and class II+ pre‐B cells did not exhibit adhesion in response to these stimuli, suggesting that cross‐linking of class II molecules generated a transmembrane signal and did not simply aggregate cells. In addition, MHC class II‐induced adhesion was Fc receptor independent, as 15 mAb of different Ig isotypes reactive with HLA‐D or HLA‐DQ gene products induced adhesion. Anti‐class II mAb and CD4‐γ3 were able to induce adhesion at concentrations as low as 10 ng/ml and 100 ng/ml, respectively. Suboptimal stimulation of B cell lines through HLA‐D antigens induced homotypic adhesion that was dependent on the activation of LFA‐1 (CD11a/CD18), and which could be blocked by specific mAb. However, at greater signal strengths, adhesion was not blocked by mAb against the known adhesion receptors, suggesting the induction of a novel adhesion pathway. Consistent with this, homotypic adhesion induced by engagement of MHC class II antigens was observed with LFA‐1‐deficient B cell lines, and was independent of CD49d or CD18 expression. Thus, the direct engagement of B cell class II antigens by CD4 is likely to generate transmembrane signals which trigger both LFA‐1‐dependent and LFA‐1‐independent adhesion pathways.
ASJC Scopus subject areas
- Immunology and Allergy