Genetic control of ligand induced events in B lymphocytes

The sequence of reactions of anti immunoglobulin (anti Ig) antibody or antigen with the surface Ig (sIg) or B lymphocytes involves an early clustering of the receptor ligand complex in an energy independent step, followed by an integrated flow of complexes to one end of the cell to form a cap, after which the cell experiences a series of contractions that leads to a brief episode of translatory motion. The complexes are then endocytosed and metabolized. This cycle of ligand induced events, which constitutes the most immediate response of the B cell to a signal at its antigen receptor, was compared in several inbred strains of mice. Kinetic differences were found in the rate of sIg capping and absolute differences in extent were found for anti Ig induced B cell motility. These strain differences were not restricted to the B cell sIg molecules, however, since capping by Con A of its receptor sites on B and T cells and random T cell motility were also affected. A genetic analysis of A and CBA mice revealed that each of the traits studied is probably affected by two gene differences between the two strains analyzed. The possible roles of microtubules and cyclic nucleotides in these genetic differences were also explored. Colchicine, which depolymerizes microtubules, raised the low capping and motile responses of CBA spleen cells to the high responses characteristic of A strain cells. This implies an excess of microtubular function in CBA cells. Raising the level of cyclic AMP also raised the low CBA capping response to the high A level, but did not differentially effect the motile responses of cells of the two strains. The possible significance and locus of action of these effects is discussed.