B Lymphopoiesis

B lymphocytes represent specialized cells of the immune system that exert complex functions after differentiating in diverse subtypes.  B lymphocytes are the main components of the humoral branch of immunity and produce antibodies after terminal differentiation in plasmacells . The knowledge of the cellular and molecular events leading to B cell formation is instrumental for the comprehension of both the immune response and the process of B cell malignant transformation. From B lymphocytes may arise tumors like acute lymphoblastic leukemia, Hodgkin's non Hodgkin's lymphomas and multiple myeloma. A dysfunctional B cell compartment is also cause of autoimmune disorders, such as systemic lupus erythematous and rheumatoid arthritis.  Lymphocyte development is thightly regulated from the early steps by the action of transcription factors, signaling pathways (like Notch, Interleukin-7/IL-7R) and likely microenvironmental instructive signals, which drive hematopoietic stem cells to the lymphoid lineage choice and generation of a common lymphoid progenitor from which T and B cell arise. B cell need the concerted activity of PU.1 (which fades down) and Ikaros, E2A and PAX5 (which goes up) transcription factors.  The precise regulation of these early steps in B-lymphopoiesis are only partly clear and the activity of these molecules can be regulated by post-tranlsational modification like phosphorylation.  Throughout B cell maturation, the signals coming from the preB-cell receptor (Pre-BCR) and, later on, the B-cell receptor (BCR) are critical for B cell survival, proliferation, maturation and differentiation in specialized B-cell subsets.  Downstream from the Pre-BCR and BCR numerous signaling pathways are activated, which mediate several developmental processes. In our laboratory we are investigating the role of serine-threonine protein kinases in B lymphocyte development and function by analyzing their role throughout B lymphopoiesis.