8-8 Immature B cells arriving in the spleen turn over rapidly and require cytokines and positive signals through the B-cell receptor for maturation and long-term survival.
Fig. 8.11 Transitional B cells that recognize self antigens undergo peripheral tolerance. After emigrating from the bone marrow and entering the circulation, immature B cells are known as transitional B cells. Not yet fully mature, these cells are still subject to tolerance in the spleen following engagement of their sIgM receptor by a self antigen. Transitional B cells that encounter a multivalent self antigen receive a strong B-cell receptor signal and undergo cell death. Transitional B cells with sIgM that binds to a soluble self molecule are rendered anergic, and ultimately die within a few days due to being excluded from the B-cell follicles in the spleen (see Fig. 8.12). Transitional B cells that bind with low affinity to a soluble self molecule remain clonally ignorant of the self antigen and continue their maturation. Transitional B cells with no self reaction also continue their maturation into mature B cells. The final stages of B-cell maturation lead to upregulation of sIgD, and take place in the B-cell follicles in the spleen.
When B cells emerge from the bone marrow into the periphery, they are still functionally immature. As discussed above, their final maturation in the periphery
Transitional B cells that enter the follicle receive maturation and survival signals and differentiate into follicular B cells or marginal zone B cells provides an opportunity for the immature B cells to encounter peripheral self antigens and to undergo tolerance. Immature B cells express high levels of sIgM but little sIgD, whereas mature B cells express low levels of IgM and high levels of IgD; while the changes in expression of sIgM and sIgD as B cells mature is well documented, the function of sIgD on mature B cells is not known.
Most immature B cells leaving the bone marrow will not survive to become fully mature B cells. Figure 8.12 shows the possible fates of newly produced B cells that enter the periphery. The daily output of new B cells from the bone marrow is roughly 5–10% of the total B-lymphocyte population in the steady-state peripheral pool. In unimmunized animals, the size of this pool seems to remain constant, due to homeostasis, which means that the stream of new B cells needs to be balanced by the removal of an equal number of peripheral B cells. However, the majority of peripheral mature B cells are long-lived, and only 1–2% of these die each day. Thus, most of the B cells that die are in the rapidly turning-over immature peripheral B-cell population, of which more than 50% die every 3 days. The failure of most newly formed B cells to survive for more than a few days in the periphery seems to be due to competition between peripheral B cells for access to the follicles in the spleen. If newly produced immature B cells do not enter a follicle, their passage through the periphery is halted and they eventually die. The limited number of lymphoid follicles cannot accommodate all of the B cells generated each day, and so there is continual competition for entry.