The properties of resting B cells, plasmablasts, and plasma cells are compared in Fig. 10.9. The differentiation of a B cell into a plasma cell is accompanied by many morphological changes that reflect a commitment to the production of large amounts of secreted antibody, which can constitute up to 20% of all the protein synthesized by a plasma cell. Plasmablasts and plasma cells have a prominent perinuclear Golgi apparatus and an extensive rough endoplasmic reticulum that is rich in immunoglobulin molecules that are being synthesized and exported into the lumen of the endoplasmic reticulum for secretion. Plasmablasts have relatively large numbers of B-cell receptors on the cell surface, whereas plasma cells have many fewer. This low level of surface immunoglobulin on plasma cells may still be physiologically important, since their survival seems to be determined in part by their ability to continue to bind antigen. Plasmablasts still express B7 co-stimulatory molecules and MHC class II molecules; by contrast, plasma cells turn down the expression of MHC class II molecules. Nevertheless, T cells still provide important signals for plasma-cell differentiation and survival, such as IL-6 and CD40 ligand.
Fig. 10.9 Plasma cells secrete antibody at a high rate but can no longer respond to antigen. Resting naive B cells have membrane-bound immunoglobulin (usually IgM and IgD) and MHC class II molecules on their surface. Although their V genes do not carry somatic mutations, B cells can take up antigen and present it to helper T cells. The T cells in return induce the B cells to proliferate and to undergo isotype switching and somatic hypermutation, but B cells do not secrete significant amounts of antibody during this period. Plasmablasts have an intermediate phenotype. They secrete antibody but retain substantial surface immunoglobulin and MHC class II molecules and so can continue to take up and present antigen to T cells. Plasmablasts early in the immune response and those activated by T-independent antigens have usually not undergone somatic hypermutation and class switching, and therefore secrete IgM. Plasma cells are terminally differentiated cells that secrete antibodies. Plasma cells have very low levels of surface immunoglobulin but can express MHC class II molecules and may suppress TFH activity in a negative feedback pathway while differentiating. Early in the immune response they differentiate from unswitched activated B cells and secrete IgM; later in the response they derive from activated B cells that entered the germinal center reaction and underwent class switching and somatic hypermutation. Plasma cells have lost the ability to change the class of their antibody or undergo further somatic hypermutation.
Naive B cells travel to the lymph node via the bloodstream and leave via the efferent lymph
Plasma cells migrate to the medullary cords or leave via the efferent lymphatics HEVfollicle germinal center primary focus B cells that encounter antigen in the follicle form a primary focus. Some proliferating B cells migrate into the follicle to form a germinal center Plasma cells migrate to the bone marrow bone marrow stromal cell
Recent evidence indicates that even the low level of MHC class II molecules expressed on plasma cells functions to present cognate antigen to TFH cells, and acts to suppress IL-21 production and Bcl-6 expression, thus acting as a feedback pathway to regulate ongoing B-cell responses. While some plasma cells survive for only days to a few weeks after their final differentiation, others are very long lived and account for the persistence of antibody responses.
10-6 The second phase of a primary B-cell immune response proliferate to form germinal centers.