Cutting Edge: Neutrophil Complement Receptor Signaling Is Required for BAFF-Dependent Humoral Responses in Mice.

Area of Science:

• Immunology
• Innate Immunity
• Complement System

Background:

• T cell-independent (TI) B cell responses to non-protein antigens rely on innate immune cues.
• Neutrophil activation and B cell responses are linked, but mechanisms are unclear.
• Neutrophils produce BAFF, a key cytokine for B cell survival and function.

Purpose of the Study:

• To elucidate the role of neutrophil complement receptors in T cell-independent (TI) B cell responses.
• To investigate the contribution of neutrophil C3a and C5a receptors to B cell activation and antibody production.
• To understand the impact of neutrophil complement signaling on mucosal IgA responses.

Main Methods:

• Utilized germline and conditional knockout mouse models.
• Investigated alternative pathway complement activation.
• Assessed B cell populations, BAFF levels, and IgA class-switching in Peyer's patches and feces.

Main Results:

• Neutrophil C3aR1/C5aR1 signaling is essential for TI humoral responses.
• Absence of these receptors on neutrophils reduced serum BAFF, Peyer's patch germinal center B cells, and IgA class-switching.
• Conditional knockout of neutrophil C3aR1/C5aR1 led to decreased fecal IgA levels.

Conclusions:

• Sequential complement activation on neutrophils is critical for TI B cell responses.
• Neutrophil complement receptors upregulate BAFF production, supporting B1 cell expansion and TI antibody production.
• This pathway is crucial for maintaining mucosal IgA homeostasis.