B lymphocytes express a receptor for a complement system protein that provides second signals for the activation of these cells (Fig. 1A). is a collection of plasma proteins that are activated by microbes and by antibodies attached to microbes and function as effector mechanisms of host defense . When the complement system is activated by a microbe as part of the innate immune response, the microbe becomes coated with proteolytic fragments of the most abundant complement protein, C3. One of these fragments is called C3d. B lymphocytes express a receptor for C3d called complement receptor type 2 (CR2, or CD21). B cells that are specific for a microbe’s antigens recognize the antigens by their BCRs and simultaneously recognize the bound C3d via the CR2 receptor. Engagement of CR2 greatly enhances antigen-dependent activation responses of B cells by enhancing tyrosine phosphorylation of ITAMs. that microbes or innate immune responses to microbes provide signals in addition to antigen that are necessary for lymphocyte activation. In humoral immunity, complement activation represents one way in which innate immunity facilitates B lymphocyte activation.

Microbial products also directly activate B cells by engaging innate pattern recognition receptors (see Fig. 1B). B lymphocytes, similar to dendritic cells and other leukocytes, express numerous Toll-like receptors (TLRs). Pathogen-associated molecular patterns bind to TLRs on the B cells, which triggers activating signals that work in concert with signals from the antigen receptor. This combination of signals stimulates B cell proliferation, differentiation, and Ig secretion, thus promoting antibody responses against microbes. 

Fig1. Role of innate immune signals in B cell activation. Signals generated during innate immune responses to microbes and some antigens cooperate with recognition of antigen by antigen receptors to initiate B cell responses. A, Activation of complement by microbes leads to the binding of a complement breakdown product, C3d, to the microbes. The B cell simultaneously recognizes a microbial antigen (by the immunoglobulin receptor) and bound C3d by CR2 (type 2 complement receptor). CR2 is attached to a com plex of proteins (CD19, CD81) that are involved in delivering activating signals to the B cell. B, Molecules derived from microbes (so-called pathogen-associated molecular patterns [PAMPs]; see Chapter 2) may activate Toll-like receptors (TLRs) of B cells at the same time as microbial antigens are being recognized by the antigen receptor. BCR, B cell receptor.