Expansion of an Antigen-Specific B-Memory Cell Population on Initial Antigen Exposure Results in a Faster, More Pervasive, Secondary Immune Response
As the host is exposed to a foreign antigen, all existing B cells that have a BCR capable of binding the foreign antigen are able to react to such an antigen. Initially, among the millions of different B cells, the BCR of a few will bind to the antigen.
This binding allows those matching B cells to multiply, creating many more B cells with the same BCR. This rather rapid expansion of antigen-specific B cells is often referred to as specific clonal expansion. The newly generated B cells start producing specific antibodies and secreting them. Specific antibodies begin appearing in circulation, and as clonal expansion increases, the quantity of specific antibodies in circulation increases. All B cells start their specific antibody production by producing IgM isotypes. Given the right milieu (e.g., appropriate sequence of signals), B cells stop producing IgM and switch production to IgG or another isotype (IgA or IgE); it is important to understand, however, that the antigenic specificity of the antibody does not change. These dynamics are consistent with Ihoseobserved in a primary and secondary immune response.As the host encounters an antigen for the first time, few of the existing B cells are able to recognize it, but once the antigen is recognized by those few B cells, they undergo clonal expansion. Therefore, antibody production starts increasing, shows up in circulation, and IgM predominates during the primary immune response. The long “lag” period represents the time needed to process significant numbers of antibodyproducing B cells through clonal expansion. Some B cells start switching to IgG production, which is why some IgG appears during the later parts of a primary immune response. As antigen is neutralized by the antibodies, B-cell stimulation stops, antibody production declines until it eventually stops, and many B cells within the expanded population become long-lived memory B cells.
If the host confronts the same antigen for a second time, the antigen is recognized by the vastly expanded, antigenspecific B-memory cell population, many cells of which have switched their antibody production capability to an isotype other than IgM, mainly IgG.
This expanded cell population starts antibody production quickly because of the larger population of antibody-producing cells and greater likelihood of being in an IgG-producing state. The lag period is therefore very short, and a large amount of IgG is produced, typical of a secondary immune response. Eventually, as in a primary immune response, clonal expansion stops, and antibody production decreases and eventually stops. Future confrontations with the same antigen will lead to secondary immune responses, which are characterized by short “lag periods” and high sustained production of IgG or other isotypes (IgA or IgE).Antigen stimulation of the BCR is not a sufficient signal to initiate B-cell clonal expansion and antibody production. Many other signals must reach the B cell after its BCR has recognized antigen. These signals, often represented by interleukins, come from Th cells that have recognized the antigen through complex interaction mechanisms with APCs (see earlier discussion). Interestingly, B cells that have bound antigen through their BCR and have internalized the BCR-bound antigen are also able to interact with Th cells, helping them to Tecognizeantigen. A B cel I-T cell interaction is also necessary for B cells to switch their production from IgM to other isotypes. The B cells must interact with interleukins from Th cells.The timing and nature of the interleukins reaching the B cells play an important role in deciding to which isotype the B cell is switching.