The ontogeny of murine B lymphocytes. I. Induction of phenotypic conversion of Ia-to Ia+ lymphocytes.

When bone marrow and spleen cells of 4 week-old mice are fractionated on a discontinuous BSA gradient, a small fraction of Ia- cells is obtained which can be induced in vitro to express the Ia alloantigen within 2 hr. This is in precise parallel to the prothymocyte induction system of Komuro and Boyse. Ia specificity is ascertained by the use of two reciprocal antisera, A.TH anti-A.TL (anti-Iak) and A.TL anti-A.TH (anti-Ias), which yield the expected reaction pattern on induced bone marrow cells of (B6 X A)F1 (Iak) and SJL/J (Ias) mice. Induction can be effected by a number of agents, such as catecholamines, prostaglandin PGE1, cAMP, bacterial endotoxin, lipid A, ubiquitin, and thymopoietin. The last requires a 100-fold higher concentration for Ia+ induction as compared to prothymocyte induction, thus implying a lower affinity for the B cell receptor than for the thymocyte receptor. Ia- to Ia+ conversion involves cells different from prothymocytes, as indicated by: 1) the specific cytolytic effect of our anti-Ia sera which were shown to be free of activity against thymocytes; 2) an additive cytolytic effect of anti-Ia and anti-Thy-1 sera; and 3) the fact that the Ia inducible cells are sensitive to pretreatment with anti-immunoglobulin and C. This finding that Ia- precursor cells are already Ig+ is of interest for the B cell ontogeny, as it implies that Ig expression precedes Ia expression.