Marginal zone B cell surface glycan receptors

Marginal zone B cell surface glycan receptors refer to a specialized group of proteins, primarily belonging to the Siglec (Sialic acid-binding immunoglobulin-like lectin) and C-type lectin families, that are expressed on the surface of marginal zone B (MZB) cells. These receptors, most notably CD22 (Siglec-2) and Siglec-10 (Siglec-G in mice), are essential for regulating B-cell activation thresholds and maintaining the homeostasis of the MZB cell population, which serves as a first line of defense against blood-borne pathogens. They function by recognizing specific glycan motifs, such as sialic acids, on both self-antigens and microbial surfaces, thereby modulating B-cell receptor (BCR) signaling and preventing autoimmunity. In clinical contexts, these receptors are significant targets in the treatment of B-cell malignancies, particularly marginal zone lymphoma, and autoimmune diseases like systemic lupus erythematosus. Therapeutic agents such as epratuzumab and inotuzumab ozogamicin specifically target CD22 to induce B-cell depletion or modulate immune responses. Additionally, these receptors play a role in the capture and processing of encapsulated bacterial antigens, making them vital for the immune response to infections.

Other names

SiglecsSialic acid-binding immunoglobulin-type lectinsB-cell glycan-binding receptorsCD22Siglec-10Siglec-GB-cell lectins

These receptors primarily function as inhibitory co-receptors that modulate B-cell receptor (BCR) signaling by recruiting phosphatases like SHP-1 to their intracellular ITIM motifs. Drugs targeting these receptors, such as anti-CD22 antibodies, work by inducing B-cell depletion through antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), or by delivering cytotoxic payloads as antibody-drug conjugates (ADCs).