816 Anti - Immunoglobulin Stimulation of Mouse Lymphocytes

Although thymus-independent (B) lymphocytes of mice bear large amounts of membrane immunoglobulin (Ig) (1), it has been difficult to demonstrate directly that membrane Ig is involved in the "signal generation" which leads to proliferation and differentiation of B lymphocytes. One of the chief arguments against membrane Ig playing a role in such ~signaling" has been the apparent failure of anti-Ig reagents to cause thymus-independent activation of B lymphocytes (2). Most investigators have failed to detect proliferation of mouse, rat, or guinea pig lymphocytes in response to anti-Ig antiserum (2-4). However, it is known that anti-Ig can initiate proliferative responses in lymphocytes from rabbits (5), chickens (6, 7), pigs (8), and humans (9-12) in at least some cases. Recently, two groups have reported initiation of proliferative responses by mouse B lymphocytes under special circumstances. Parker (13) reported that polyacrylamide beads coated with anti-Ig, but not soluble anti-Ig, caused uptake of 125I-deoxyuridine by splenic B lymphocytes. Weiner et al. (14) have recently described stimulation of splenic lymphocytes from mice older than 5 mo of age by anti-Ig antiserum, but have failed to obtain proliferative responses with spleen cells from normal young adult mice. In the Parker system, no synthesis of Ig as a result of anti-Ig stimulation could be detected. Because of the potential importance of anti-Ig as a probe to explore requirements for B-cell activation, we have reinvestigated this problem using highly purified goat antibodies directed at mouse ~and K-determinants. Our results demonstrate that such reagents, particularly anti-~t, are potent mitogenic stimulants for lymphocytes from young adult mice. In this communication we describe the purity of the reagents and the parameters of stimulation. In a forthcoming paper, we will show that this is a T-independent response and that it very likely involves a subset of mature B lymphocytes.