CD20

CD20 is a transmembrane protein found on the surface of B lymphocytes, beginning at the pre-B cell stage and persisting through mature B cell differentiation, but it is notably absent on early pro-B cells, plasma cells, and hematopoietic stem cells—this makes it a useful immunohistochemical marker to identify B-cell lineage and distinguish B-cell neoplasms from T-cell neoplasms. Functionally, CD20 is thought to act as a store-operated calcium channel that plays a role in B cell receptor signaling, activation, proliferation, and differentiation, though its exact physiologic ligand remains unknown. Clinically, CD20 is most significant as the target of rituximab, a chimeric monoclonal antibody that causes B cell depletion via complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and induction of apoptosis. Rituximab and other anti-CD20 agents (e.g., obinutuzumab, ofatumumab) are used in the treatment of non-Hodgkin lymphoma (especially diffuse large B-cell lymphoma and follicular lymphoma), chronic lymphocytic leukemia, and autoimmune conditions such as rheumatoid arthritis, ANCA-associated vasculitis, and some cases of lupus nephritis. Because CD20 is not expressed on stem cells or plasma cells, B cell depletion therapy spares long-term antibody production from plasma cells while allowing eventual B cell repopulation from CD20-negative progenitors. Flow cytometry and immunohistochemistry for CD20 are essential diagnostic tools in classifying lymphomas and leukemias of B-cell origin (e.g., CD20+ in most B-cell lymphomas, contrasted with CD3+ T-cell lymphomas). Monitoring CD20 expression is also relevant because some relapsed lymphomas can lose CD20 expression, leading to resistance to anti-CD20 therapy.