Identification of novel genes that regulate B-1 cells

Abstract

Abstract IgM is the first antibody produced in ontogeny and in response to an initial antigen exposure. It plays an important role in effective immune protection, and is required for maximal antigen-specific IgG responses. In mice, most circulating serum IgM is generated by fetal-derived B-1 cells in spleen and bone marrow. How B-1 cells preferentially develop into natural IgM secreting cells is incompletely understood. To identify candidate genes critical for B-1 cells development and/or maintenance we generated parts of a larger immunophenotyping database Knock Out Mouse Project (KOMP) providing results of the flow cytometric evaluation of spleen cells from 641 mouse strains, each containing a single-gene deletion as well as 200 individual congenic control mice, identifying 58 distinct leukocyte subsets for each spleen. We generated and curated a complete list of each gene found to be associated with B-1 cell changes. Seven genes were identified that significantly reduced frequencies of CD5+ B-1 cells in males and/or females, of which three were uniquely altering the B-1 cell subset. None of these genes have been associated with B-1 cell regulation previously. Using qRT-PCR we found that 4 showed B-1 cell intrinsic gene expression. Ongoing work is to determine the impact of each gene on serum antibody levels and immune protection to influenza virus challenge. This work was supported by NIH UM1 OD023221 (KCKL), R0AI148652 (NB), and the Graduate Student Support Program UC Davis (SR).