248 PART I Generation of B-Cell and T-Cell Responses VISUALIZING CONCEPTS ANTIGEN-INDEPENDENT PHASE CD45R Selection> Bone marrow marker ANTIGEN-DEPENDENT PHASE Tu cll +ag (-10% Cell death Activated (-90% Affinity Plasma FIGURE 11-1 Overview of B-cell development. During the anti- tivated TH cells. Once activated, B cells proliferate within sec- gen-independent maturation phase, immunocompetent B cells ondary lymphoid organs. Those bearing high-affinity mlg differ expressing membrane igM and igD are generated in the bone entiate into plasma cells and memory B cells, which may express marrow. Only about 10% of the potential B cells reach maturity different isotypes because of class switching. The numbers cited and exit the bone marrow. Naive B cells in the periphery die within refer to B-cell development in the mouse, but the overall princi a few days unless they encounter soluble protein antigen and ac- ples apply to humans as well Progenitor B Cells Proliferate shaft of a bone. Proliferation and differentiation of pro-B in Bone marrow cells into precursor B cells(pre-B cells)requires the micro environment provided by the bone-marrow stromal cells. If B-cell development begins as lymphoid stem cells differenti- pro-B cells are removed from the bone marrow and cultured ate into the earliest distinctive B-lineage cell-the progeni-. in vitro, they will not progress to more mature B-cell stage tor B cell (pro-B cell)which expresses a transmembrane unless stromal cells are present. The stromal cells play two tyrosine phosphatase called CD45R(sometimes called B220 important roles: they interact directly with pro-B and pre-B in mice). Pro-B cells proliferate within the bone marrow, fill- cells, and they secrete various cytokines, notably IL-7, that ing the extravascular spaces between large sinusoids in the support the developmental processProgenitor B Cells Proliferate in Bone Marrow B-cell development begins as lymphoid stem cells differenti￾ate into the earliest distinctive B-lineage cell—the progeni￾tor B cell (pro-B cell)—which expresses a transmembrane tyrosine phosphatase called CD45R (sometimes called B220 in mice). Pro-B cells proliferate within the bone marrow, fill￾ing the extravascular spaces between large sinusoids in the shaft of a bone. Proliferation and differentiation of pro-B cells into precursor B cells (pre-B cells) requires the micro￾environment provided by the bone-marrow stromal cells. If pro-B cells are removed from the bone marrow and cultured in vitro, they will not progress to more mature B-cell stages unless stromal cells are present. The stromal cells play two important roles: they interact directly with pro-B and pre-B cells, and they secrete various cytokines, notably IL-7, that support the developmental process. 248 PART II Generation of B-Cell and T-Cell Responses VISUALIZING CONCEPTS ~5 × 106 per day Bone marrow CD45R (B220) surface marker Peripheral lymphoid organ Plasma cell Ig-gene rearrangement Selection Progenitor B cell Mature B cell Secreted Ab Cell death (~90%) Memory B cell Activated B cell Affinity maturation Class switching TH cell –Ag +Ag (~10%) Naive B cell ANTIGEN-INDEPENDENT PHASE (maturation) ANTIGEN-DEPENDENT PHASE (activation and differentiation) FIGURE 11-1 Overview of B-cell development. During the anti￾gen-independent maturation phase, immunocompetent B cells expressing membrane IgM and IgD are generated in the bone marrow. Only about 10% of the potential B cells reach maturity and exit the bone marrow. Naive B cells in the periphery die within a few days unless they encounter soluble protein antigen and ac￾tivated TH cells. Once activated, B cells proliferate within sec￾ondary lymphoid organs. Those bearing high-affinity mIg differ￾entiate into plasma cells and memory B cells, which may express different isotypes because of class switching. The numbers cited refer to B-cell development in the mouse, but the overall princi￾ples apply to humans as well