The role of Apobec3 enzymes in regulation of marginal zone B cells The Apobec3 enzymes are intensely studied restriction factors of exogenous and endogenous retroelements (retroviruses and retrotransposons). Endogenous retroelements make up almost half of the mouse and human genomes-many of them somatically active. They often are interspersed within cellular genes and are thus transcribed along with cellular genes. Unrestricted retroelements can cause inflammation and, via insertional mutagenesis, cancer, but the innate and adaptive immune systems keep most of them in check. We found that Apobec3 enzymes decrease, in an activity-graded manner, the number of marginal zone B cells of mice, but not the number of follicular B cells or T cells. We, therefore, suggest that endogenous retroelements drive the development and/or expansion of the marginal zone B-cell population. In this grant application, we propose to test whether the retroelements activity is intrinsic to the marginal zone B cells, and to identify the retroelements
The role of Apobec3 enzymes in regulation of marginal zone B cells The spleen is made up of white pulp and red pulp, separated by the marginal zone, which is populated by specialized lymphocytes that produce antibodies in a fast first response to blood-borne pathogens. We found that the development of these lymphocytes is controlled by enzymes that inhibit retrovirus-like segments in the genome;this grant application seeks to identify the relevant DNA segments and their role in marginal zone lymphocyte development.
| Beck-Engeser, Gabriele B; Winkelmann, Rebecca; Wheeler, Matthew L et al. (2015) APOBEC3 enzymes restrict marginal zone B cells. Eur J Immunol 45:695-704 |
