lgGPlasmablast and plasma cell lgG Memory B cell CD135 Plasma cell antigen-1 CD38 Somatic hypermutation VJ rearranged Isotype switch to C˜, C°, or C˛. Somatic hypermutation Alternative splicing yields both membrane and secreted Ig lgM Lympho-blast lgMlgD Mature naive B cell CD45R MHC class II IgM, IgD CD19, CD20 CD21, CD40 CD45R MHC class II IgG, IgA CD19, CD20 CD21, CD40 CD45R MHC class II CD19, CD20 CD21, CD40 VDJ rearranged. ˝chain produced in membrane form. Alternative splicing yields ˝+ˆmRNA Alternative splicing yields secreted ˝chains Ig IgANTIGENDEPENDENTTERMINALDIFFERENTIATIONCD45R AA4.1, IL-7R MHC class II pre-B-R CD19, CD38 CD20, CD40 CD45R AA4.1 MHC class II CD19, CD38 CD20, CD40 Germline pre-B-cell receptor cytoplasmic ˝˝RAG-1 RAG-2 Large pre-B cell Small pre-B cell Late pro-B cell Germline TdT ˇ5, VpreB ˇ5, VpreB CD45R AA4.1, IL-7R MHC class II CD10, CD19 CD38, CD20 CD40 D–J rearranged V–DJ rearranged VDJ rearranged VDJ rearranged V–J rearrangement Early pro-B cell Stem cell Germline Germline Germline RAG-1 RAG-2 TdT ˇ5, VpreB CD34 CD45 AA4.1 CD34 CD45R AA4.1, IL-7R MHC class II CD10, CD19 CD38 Heavy-chain genesB cells Light-chain genes Intra-cellular proteins Surface marker proteinsANTIGENINDEPENDENT rearranged.
AA4.1
CD19, CD20
Development of T lymphocytes.
Like B cells, T lymphocytes derive from the multipotent hematopoietic stem cells in the bone marrow. However, their progenitor cells migrate from the bone marrow via the blood to the thymus, where they mature (Fig. 8.15); this is the reason for the name thymus-dependent (T) lymphocytes, or T cells. T-cell development parallels that of B cells in many ways, including the orderly and stepwise rearrangement of antigen-receptor genes, the sequential testing for successful gene rearrangement, and the eventual assembly of a heterodimeric antigen receptor. Nevertheless, T-cell development in the thymus has some features not seen for B cells, such as the generation of two distinct lineages of T cells expressing antigen receptors encoded by distinct genes, the γ:δ lineage and the α:β lineage. Developing T cells, which are known generally as thymocytes, also undergo rigorous selection that depends on interactions with thymic cells and that shapes the mature repertoire of T cells to ensure self MHC restriction as well as self-tolerance. We begin with a general overview of the stages of thymocyte development and its relationship to thymic anatomy before considering gene rearrangement and the mechanisms of selection.
8-10 T-cell progenitors originate in the bone marrow, but all the important events in their development occur in the thymus.