Types of lymphocytes

What are the two main types of lymphocytes? How are they differentiated? What are their subtypes?

• T lymphocytes, or T cells, are hymus-derived and express the TCR-CD3 complex on their surface. They can be separated from other lymphocytes by the use of monoclonal antibodies that recognize CD3, a component of the TCR that transduces the TCR signal across the lymphocyte membrane. T-cell subtypes include:

• CD4+ T cells: Th1, Th2, Th17, regulatory T cells (Tregs), follicular T helper cells (Tfh).

• CD8+ T cells: cytotoxic T lymphocytes (CTLs).

• Natural killer T cells (NKT): T cells that express NK cell markers and have restricted TCRs that recognize lipids bound to the MHC-like molecule CD1d.

• Gamma-delta T cells: use γ- and δ-chains to form the TCR. Most are double negative (lack CD4 and CD8). They make up 2% to 3% of circulating T cells and are primarily found in the skin and gut epithelium. These TCRs do not recognize antigen in context with MHC but rather recognize antigen directly or in association with MHC class I-like molecules such as CD1 (binds glycolipid antigens) and MICA/MICB in the gut. HSPs can directly activate these cells. They interact with alkyl phosphates found in mycobacteria and are expanded during certain infections. Notably, they are expanded in the small intestinal epithelium of individuals with celiac disease.

• B lymphocytes, or B cells, are one marrow-derived antibody-secreting cells that express surface Ig (e.g., B-cell receptor [BCR]) on their surfaces. There are several subpopulations of B cells:

• B1 cells develop earliest during ontogeny and are characterized as innate-like B cells. Most express CD5. They are activated by microbes through PRR, do not require T-cell help, do not develop into memory B cells, and are the source of “natural” antibodies. These antibodies are low affinity, IgM, and polyreactive, recognizing both common pathogens and autoantigens. They are located predominantly in peritoneal and pleural cavities.

• B2 cells develop later in ontogeny and lack CD5 surface marker. Before encountering antigen, mature B2 cells coexpress IgM and IgD antibodies on their surfaces. With antigen stimulation and T-cell help, they secrete highly specific antibody (IgM, IgG, IgA, or IgE) within the secondary lymphoid tissue. Follicular B cells can freely circulate and are organized into the primary follicles of B-cell zones focused around follicular dendritic cells (FDCs) in the white pulp of the spleen and the cortical areas of peripheral lymph nodes. They comprise 95% of B cells in lymph nodes and spleen. Marginal zone B cells are noncirculating B cells that are located in the marginal zone of the spleen. Memory B cells are CD27+, constitute 1% of total B-cell population, and can be long-lived (years) with continued antigen stimulation. Plasma cells are terminally differentiated B cells that function to secrete antibody.

• Regulatory B cells (Bregs, B10) subsets are found within the B1 and B2 populations. They secrete IL-10 to modulate the immune response.

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