T cell-dependent, B cell-activating properties of antibody-coated small latex beads. A new model for B cell activation.

Abstract

We have developed a new model to study B cell activation induced by complex particulate Ag, immune complexes, and viruses. As the surrogate for such Ag, we have used 100-nm fluorescent latex beads bearing mAb to IgM and IgD. Anti-IgM- and anti-IgD-coated small latex beads bind readily to tonsil resting B cells and induce homotypic B cell aggregation. Aggregation induced by anti-IgM-coated beads but not by anti-IgD-coated beads was massively enhanced by IL-2 and IL-4. Anti-IgM- and anti-IgD-coated beads increased (4- to 12-fold) c-fos and c-myc mRNA levels in resting B cells in a dose-dependent manner; this increase was tyrosine kinase dependent. Anti-IgM- and anti-IgD-coated beads were mitogenic for resting B cells, but unlike other B cell activation models, mitogenesis was absolutely dependent on the presence of IL-2 or IL-4. Finally, anti-IgM-coated beads but not anti-IgD-coated beads were internalized as single beads into small, thin-walled endocytic vesicles; internalization was absolutely dependent on the presence of IL-4. Binding and internalization can be readily quantified because the beads are fluorescent. This model can also be used to study the functions of other cell surface molecules that modulate Ag-specific B cell immune responses. It will also be used for examining multiple aspects of T-B cell interactions during immune responses and Ag processing because of the dependence on T cell factors for B cell activation, coupled with the finding that the Ab-coated beads are internalized.