B Cell Dynamics within the Bone Marrow Microenvironment: Comparisons of Inflammation and Steady State

For adult mice and humans the bone marrow is of critical importance in the generation and function of B lymphocytes. It is here that B cells are born from early hematopoietic progenitors; and where the first selection checkpoints occur to enforce central tolerance. Moreover, the bone marrow exhibits characteristics reminiscent of a secondary lymphoid organ, providing a home for a large population of recirculating mature B cells; these cells are capable of mounting rapid immune responses against blood borne pathogens, in situ. The bone marrowâ s ability to support these diverse functions is highly dependent on its organized structure and complex microenvironment. Multiple cell types and soluble cytokines are involved in regulating hematopoietic and immunological activities and the characterization of these factors remains an active area of research. However, peripheral signals, such as inflammation, are capable of modulating the bone marrow microenvironment with a dramatic effect on B cells. Herein, data is presented detailing how acute peritoneal inflammation and breast cancer can each alter the bone marrow environment to shape the B cell compartment. Further, experiments are described that suggest a role for basophils in aiding immature B cell survival and maturation in steady state and inflammation. Together these findings characterize novel environmental components important in B cell development and highlight the exquisite sensitivity of the bone marrow organ to peripheral cues.Ph.D