Thymus-Dependent Antigen

Thymus-Independent Antigen

Chemical nature


Polymeric antigens, especially polysaccharides; also glycolipids, nucleic acids

Features of Antibody Response

Isotype switching

Yes; IgG, IgE, and IgA

Little or no; may be some IgG and IgA

Affinity maturation



Secondary response (memory B cells)


Only seen with some antigens (e.g., polysaccharides)

Although TI responses typically show little isotype switching, some T-independent nonprotein antigens do induce Ig isotypes other than IgM. In humans, the dominant antibody class induced by pneumococcal capsular polysaccharide is IgG2. In mice engineered to lack CD40, IgE and many IgG subclasses are barely detectable in the serum, but levels of IgG3 (which resembles human IgG2) and IgA in the serum are reduced to only about half their normal levels. Cytokines produced by non-T cells may stimulate isotype switching in TI responses. As described earlier, in the absence of T cells, BAFF and APRIL produced by cells of myeloid origin, such as dendritic cells and macrophages, can induce the synthesis of AID in antigen-activated B cells through a receptor of the BAFF receptor family called TACI. This may be further facilitated by the activation of TLRs on these B cells. In addition, cytokines such as TGF-P that help mediate the IgA switch are secreted by many nonlymphoid cells at mucosal sites and may contribute to the generation of IgA antibodies directed against nonprotein antigens.

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