chapter  4
38 Pages

B-Cell Differentiation and IgE Synthesis

B lymphocytes represent less than 10% of lymphocytes in lung tissue and BAL £uid. The majority of B cells can be found in the bone marrow and lymphoid organs. B lymphocytes originate from the bone marrow and leave as surface IgM-and IgD-positive naive B lymphocytes to secondary lymphoid organs such as the spleen and lymph nodes. Here they recognize antigens through cross-linking of their surface B-cell receptor (BCR) and become activated by dendritic cells (DCs) and Tcells in theT-cell area (Fig. 1). As a result of BCR cross-linking, B cells enter into cell cycle, and demonstrate increased survival by expression of anti-apoptotic proteins. The antigen is endocytosed and presented as small peptides on MHC class II molecules, together with CD80 and CD86 molecules to activated T cells. Activated B cells also have increased expression of cytokine receptors for IL-2 and IL-4 and express CD40, so that they become receptive to T-cell-derived cytokines and CD40L. These interactions betweenTcells and B cells occur in the outer zones of theT-cell area, in close proximity to B-cell follicles. Following activation by BCR cross-linking andT-cell signals in the outerT-cell zone,B cells initiate isotype class switching (1,2). They di¡erentiate into either short-lived marginal zone plasma cells or migrate to the B-cell follicles to proliferate in the germinal center reaction (Fig.1). In the germinal center, B cells receive activating signals from follicular DCs (FDC) and helper T cells, and isotype switching proceeds further. This process is followed by somatic hypermutation and a⁄nity maturation.Those B cells with the highest a⁄nity for antigen receive survival signals from FDCs to become long-lived high-a⁄nity memory B cells or high-a⁄nity plasma cells

84 Hammad and Lambrecht

that produce high levels of immunoglobulins. The low-a⁄nity cells die by a process of programmed cell death (apoptosis) and are cleared from the follicles. Plasma cells migrate to the bone marrow, a dominant site of antibody production, whereas memory B cells recirculate throughout the body and become plasma cells upon repeated encounter with antigen.