Transforming Growth Factor Beta (TGFβ) Directs IgA1 and IgA2 Switching in Human Naive B Cells

Abstract

Until recently, there was no experimental system that permitted the study of soluble factors capable of inducing human B lymphocytes to switch isotypes in vitro. Unlike lipopolysaccharide which is currently used for murine B cells, most of human B cell activators are poorly efficient. However, two novel experimental procedures are now available: one is based on the capacity of activated T cells or their membranes to elicit a B cell response which involves interactions in surface molecules.¹ The other one, which is referred to as the CD40 system was developed in our laboratory.² In this “CD40 system”, polyclonal activation and sustained proliferation of human B cells³ are obtained by presentation of an anti-CD40 monoclonal antibody on an irradiated mouse fibroblastic L cell line that stably expresses CDw32 (FcγRII). Upon interaction with the CD40 molecule, the Fc portion of the antibody undergoes spatial rearrangement which allows high-affinity interaction with CDw32. One can further enhance the B cell response by coupling the anti-CD40 stimulation with surface Ig (slg) cross-linking agents such as anti-µ or S. aureus Cowan (SAC) particles (Fig. 1).