Original Antigenic Sin - in B Cells

In B Cells

During a primary infection, long-lived memory B cells are generated, which remain in the body, and provide protection from subsequent infections. These memory B cells respond to specific epitopes on the surface of viral proteins in order to produce antigen-specific antibodies, and are able to respond to infection much faster than B cells are able to respond to novel antigens. This effect shortens the amount of time required to clear subsequent infections.

Between primary and secondary infections, or following vaccination, a virus may undergo antigenic drift, in which the viral surface proteins (the epitopes) are altered through natural mutation, allowing the virus to escape the immune system. When this happens, the altered virus preferentially reactivates previously activated high-affinity memory B cells and spur antibody production. However, the antibodies produced by these B cells generally ineffectively bind to the altered epitopes. In addition, these antibodies inhibit the activation of lower-affinity naive B cells that would be able to make more effective antibodies to the second virus. This leads to a less effective immune response and recurrent infections may take longer to clear.

Original antigenic sin is of particular importance in the application of vaccines. The specificity and the quality of the immune response is often diminished in individuals who are repeatedly immunized (by vaccination or recurrent infections). However, the impact of antigenic sin on protection has not been well established, and appears to differ with each infectious agent vaccine, geographic location, and age. .