Fig. 8.13 A comparison of the properties of B-1 cells, follicular B cells (B-2 cells), and marginal zone B cells. In addition to developing in the liver, B-1 cells can develop in unusual sites in the fetus, such as the omentum. B-1 cells predominate in the young animal, although they probably can be produced throughout life. Being produced mainly during fetal and neonatal life, their rearranged variable-region sequences contain few N-nucleotides. In contrast, marginal zone B cells accumulate after birth and do not reach peak levels in the mouse until 8 weeks of age. Follicular B-2 cells and marginal zone B cells share a common precursor population, the transitional T2 B cells in the spleen; as a consequence, both subsets are dependent on IL-7 and BAFF signals for their development. In contrast, B-1 cell development does not require IL-7 or BAFF. B-1 cells are best thought of as a partly activated self-renewing pool of lymphocytes that are selected by ubiquitous self and foreign antigens. Because of this selection, and possibly because the cells are produced early in life, the B-1 cells have a restricted repertoire of variable regions and antigen-binding specificities. Marginal zone B cells also have a restricted repertoire of V-region specificities that may be selected by a set of antigens similar to those that select B-1 cells. B-1 cells seem to be the major population of B cells in certain body cavities, most probably because of exposure at these sites to antigens that drive B-1 cell proliferation. Marginal zone B cells remain in the marginal zone of the spleen and are not thought to recirculate. Partial activation of B-1 cells leads to the secretion of mainly IgM antibody; B-1 cells contribute much of the IgM that circulates in the blood. The limited diversity of both the B-1 and marginal zone B-cell repertoire and the propensity of these cells to react with common bacterial carbohydrate antigens suggest that they carry out a more primitive, less adaptive immune response than follicular B cells (B-2 cells). In this regard they are comparable to γ:δ T cells.
Fig. 8.14 A summary of the development of human conventional B-lineage cells. The state of the immunoglobulin genes, the expression of some essential intracellular proteins, and the expression of some cell-surface molecules are shown for successive stages of conventional B-2 B-cell development. During antigen-driven B-cell differentiation, the immunoglobulin genes undergo further changes, such as class switching and somatic hypermutation (see Chapter 5), which are evident in the immunoglobulins produced by memory cells and plasma cells. These antigen-dependent stages are described in more detail in Chapter 9.