Roles for Myb in the development and survival of murine B lymphocytes

The c-Myb transcription factor is crucial during determinant hematopoiesis and previous work has suggested it may be important for B cell development and function. However, determining what role c-Myb might have in B cells has been complicated by the embryonic lethality of the homozygous null Myb mouse. Therefore, we used tissue-specific deletion to study its role in B-lineage cells. We find that the loss of Myb results in a block in the transition from the pro-B to pre-B cell stage of development in the bone marrow and in decreased production of pre-B and immature B cells. Despite only having ∼15% the normal number of immature B cells, spleens of these mice contain 50% the normal number of B cells. Closer examination of the peripheral B cell populations demonstrated a decrease in the numbers of transitional B cells, follicular (FO) B cells, and peritoneal B1B cells. However, the number of marginal zone (MZ) B cells appears unaffected in these mice. These results suggest that c-Myb may be more important for the development and/or maintenance of transitional, follicular, and B1B cells than MZ B cells.; Expression of Myb has been associated with proliferation in a number of cell types, particularly lymphocytes. However, we find that Myb expression is not required for homeostatic B cell proliferation in vivo. Further, we find that c-Myb-deficient B cells are able to proliferate in response to a number of B cell mitogens in vitro. Myb expression has also been associated with prevention of apoptosis and we find that loss of Myb results in decreased B cell survival that appears to be due to an inability to properly respond to survival signals in vivo. We find that c-Myb-deficient B cells have decreased expression of BLyS Receptor 3 (BR3), the receptor for the survival factor BLyS. This decreased BR3 expression is accompanied by hyporesponsiveness to BLyS in vitro and defective regulation of Protein Kinase C8 (PKC8) nuclear translocation, and suggests that c-Myb is important for maintaining peripheral B cell homeostasis. Thus, c-Myb is important during multiple stages of B lymphopoiesis.