This first interaction between T and B cells not only provides important help to B cells, but also influences T-cell differentiation by signals provided by the B cell. Activated B cells express ICOSL, a member of the B7 family of co-stimulatory molecules and a ligand for ICOS (inducible co-stimulatory protein), which is expressed by T cells. This Tand B-cell interaction, provided by linked recognition, activates ICOS signaling in T cells and is important for the completion of TFH differentiation (see Section 7-21), leading to induction of the transcription factors Bcl-6 and c-Maf. These transcription factors are required for SAP production and the consequent sustained contact between B and TFH cells.
10-5 Activated B cells differentiate into antibody-secreting plasmablasts and plasma cells.
After their initial encounter, B cells that have received T-cell help migrate from the follicle border to continue to proliferate and differentiate. Two to three days after activation, B cells begin to decrease expression of CCR7 and to increase expression of EBI2 (see Fig. 10.5). Decreased expression of CCR7 causes B cells to move away from the boundary with the T-cell zone: EBI2 directs their migration back to the interfollicular regions and the subcapsular sinus in the lymph nodes, or, in the spleen, to the splenic bridging channels, a region between the T-cell area and the red pulp. Here, some B cells will form an emerging aggregate of differentiating B cells called the primary focus, which in lymph nodes is located in the medullary cords, where lymph drains out of the node, and in the spleen can be seen as extrafollicular foci in the splenic red pulp. Primary foci are apparent by about 5 days after an infection or immunization with an antigen not previously encountered.
B cells proliferate in the primary focus for several days, and this constitutes the first phase of the primary humoral immune response. Some of these proliferating B cells differentiate into antibody-synthesizing plasmablasts in the primary focus. Not all B cells activated by the initial interaction with TFH cells will move into the primary focus. Some will migrate into the lymphoid follicle, where they may eventually differentiate into plasma cells, as described below. Plasmablasts are cells that have begun to secrete antibody, yet are still dividing and express many of the characteristics of activated B cells that allow their interaction with T cells. After a few more days, the plasmablasts in the primary focus stop dividing and may eventually die. Subsequently, long-lived plasma cells will develop and migrate to the bone marrow, where they will continue antibody production. Since many long-lived plasma cells are generated long after the primary focus has dissipated, it is likely that they do not arise directly from plasmablasts in the primary focus, but rather from B cells that entered the germinal center reaction.