Distinct Profiles of Human B Cell Effector Cytokines: A Role in Immune Regulation?

TLDR

B cells are increasingly recognized as regulators of immune responses, with animal studies indicating that B cell–derived cytokines modulate immunity, yet the human factors controlling such cytokine production remain poorly understood. Human B cells produce cytokines in a context‑dependent manner: sequential BCR and CD40 stimulation induces proliferation and secretion of TNF‑α, lymphotoxin, and IL‑6 that amplify immune responses, whereas CD40 stimulation alone elicits little pro‑inflammatory cytokines but robust IL‑10 production that suppresses inappropriate responses, revealing a reciprocal regulatory paradigm.

Abstract

Abstract There is growing interest in the fundamental roles that B cells may play in regulating immune responses. Emerging animal studies point to an important contribution of B cell effector cytokines to immune modulation, yet little is known about the factors regulating such cytokine production. We report that the profile of human B cell cytokine production is context dependent, being critically influenced by the balance of signals through the B cell receptor and CD40. B cells appropriately stimulated by sequential B cell receptor and CD40 stimulation proliferate and secrete TNF-α, lymphotoxin, and IL-6, which can act not only as autocrine growth and differentiation factors, but also serve to amplify the ongoing immune response. In contrast, CD40 stimulation alone, a mimic of a B cell receiving bystander T cell help in the absence of specific Ag recognition, induces negligible proinflammatory cytokines, but significant production of IL-10 that serves to suppress inappropriate immune responses. We thus describe a novel paradigm of reciprocal regulation of B cell effector cytokines, and ascribe active roles for human B cells in either promoting or suppressing local immune responses through context-dependent cytokine production.