Regulation of B-1 lymphocyte trafficking through the C5a/C5aR1 axis
Final Report Abstract
B-1 cells are a subtype of B lymphocytes that belong to the innate immune system. As producers of natural and specific antibodies, they contribute to a rapid first-line of defense against invading pathogens, but also to homeostasis. The secreted antibodies activate the complement system, a key component of innate immunity. This cascade leads to opsonization, cell lysis, and anaphylatoxin release. The complement system significantly influences B-1 cell biology, with C5a and its receptor C5aR1 playing crucial roles in B-1 cell tissue distribution, migration, and antibody production. In this study, we compared wild-type (WT) mice with systemic C5ar1–/–, myeloid-specific (LysMcre) C5ar1–/–, and B cell-specific (CD19cre) C5ar1–/– mice to examine the direct and indirect effects of C5aR1 expression on B-1 cell biology. This approach aimed to distinguish between the impact of C5aR1 expression on B-1 cells themselves and on macrophages, which regulate B-1 cell migration through CXCL13 production. Under homeostatic conditions, no change in B-1 cell numbers and CXCL13 levels in the body cavities was observed in the four investigated mouse lines, whereas increased cell numbers were found in the spleen and omentum in systemic C5ar1–/– mice compared to WT mice but not in LysMcre C5ar1–/– and CD19cre C5ar1–/– mice. This suggests that C5aR1-mediated signaling in either LysM+ or CD19+ cells alone is not responsible for the higher B-1 cell numbers in these organs. However, nAB titers were clearly increased in systemic C5ar1–/– and CD19cre C5ar1–/– mice due to the direct influence of C5aR1 expression on CD19+ cells. TLR2/1 stimulation of peritoneal B-1 cells led to C5aR1-dependent migration to secondary lymphoid organs in WT mice, but not in C5ar1–/– or LysMcre C5ar1–/– mice. However, the C5a/C5aR1 axis did not affect B-1 cell function, as evidenced by similar IgM and nAB levels across mouse lines. Further research is needed to elucidate the mechanisms and impact of the C5a/C5aR1 axis on B-1 cell biology in steady-state and inflammatory conditions.
