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 on the surface of mu-negative proB cell lines in association with calnexin. The cross-linking of Ig beta on proB cells freshly isolated from bone marrow of recombination activating gene (RAG)-2-deficient mice induced a rapid and transient tyrosine-phosphorylation of Ig alpha as well as an array of intracellular proteins including Syk, PI3-kinase, Vav, 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 were treated with anti-Ig beta monoclonal antibody, developmentally arrested proB cells were induced to differentiate to the small preB cell stage as observed when the mu transgene was expressed in RAG-P-deficient mice. Thus, the cross-linking of Ig beta on proB cells appears to elicit differentiation signals analogous to those delivered by the preB cell receptor in normal B cell development.