THE IG-ALPHA IG-BETA HETERODIMER ON MU-NEGATIVE PROB CELLS IS COMPETENT FOR TRANSDUCING SIGNALS TO INDUCE EARLY B-CELL DIFFERENTIATION/

The immunoglobulin alpha (Ig alpha)/Ig beta heterodimer was detected o n the surface of mu-negative proB cell lines in association with calne xin. The cross-linking of Ig beta on proB cells freshly isolated from bone marrow of recombination activating gene (RAG)-2-deficient mice in duced a rapid and transient tyrosine-phosphorylation of Ig alpha as we ll as an array of intracellular proteins including Syk, PI3-kinase, Va v, and SLP-76. It also elicited the phosphorylation and activation of a MAP kinase ERK but not JNK/SAPK or p38. When RAG-2-deficient mice we re treated with anti-Ig beta monoclonal antibody, developmentally arre sted proB cells were induced to differentiate to the small preB cell s tage as observed when the mu transgene was expressed in RAG-P-deficien t mice. Thus, the cross-linking of Ig beta on proB cells appears to el icit differentiation signals analogous to those delivered by the preB cell receptor in normal B cell development.