The Sequence of Events During T Cell Dependent Antibody Responses

Protein antigens are recognized by specific B and T lymphocytes in peripheral lymphoid organs, and the activated cell populations come together in these organs to initiate humoral immune responses (Fig. 11-7). The interaction between helper T cells and B lymphocytes is initiated by the recognition of protein antigens, and the sequence of events that drive B cell proliferation and differentiation is as follows:

• Antigen is taken up by dendritic cells that have also been activated by microbial products and presented to naive helper T cells in the T cell zones of lymphoid organs.

• Helper T cells are initially activated by the dendritic cells presenting antigenic peptides on class II MHC molecules and also expressing costimulatory ligands such as the B7 molecules (see Chapters 6 and 9).

• Activated helper T cells express CD40L and also che-mokine receptors that promote their migration toward the follicle following a chemokine gradient.

• B cells in the lymphoid follicles are activated by antigen, which may be in soluble form or displayed by other cells.

• B cells process and present the antigen, alter their cell surface chemokine receptor profile, and migrate toward the T cell zone.

• Activated helper T cells and B cells interact at the boundary of the T cell zone and follicle, where the B cells are activated by CD40L on the helper T cells and by cytokines that the T cells secrete.

• Small extrafollicular B cell foci form in the medulla of the lymph node or between the periarteriolar lym-phoid sheath and the red pulp of the spleen. B cells in these foci undergo low levels of isotype switching and somatic mutation and generate short-lived plasma cells that secrete antibodies.

Lymph node

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