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108          ParT ONE  Principles of Immune Response


                               Fetal liver                                  Periphery
                               Bone marrow
                                       Antigen               Subject to            Antigen
                                      independent          antigen selection      dependent
                                                     MψLC          M     M     M
                                       TdT     µ      µ      µ             D
                                                                                                 Ig


                                Stem   ProB      Early      Late  Immature Mature  Activated  Plasma
                                 cell  cell     preB cell  preB cell  B cell  B cell  B cell  cell
                              TdT
                        VpreB, λ14.1
                            Ig α, β
                       DQ52→J(fetal)
                             D→J
                            V→DJ
                             V→J
                              slg
                             CD34
                             CD10
                             CD19
                             CD20
                             CD21
                             CD24
                             CD38
                       FIG 7.1  Model of B-Cell Differentiation. B-cell development is typically viewed as a linear progres-
                       sion through different stages of differentiation. The various processes associated with the assembly
                       of the B-cell receptor (BCR) complex and the expression pattern of surface molecules whose
                       presence or absence are illustrated through use of bars. The various steps in immunoglobulin
                       (Ig) rearrangement and the pattern of expression of these surface molecules can be used to
                       characterize stages in B-cell development.







                                                                           M
                                                                               D
                                                                                  G, A, E
                       M        M        M        M       M
                                    D       D        D        D



                                                                         Memory
                                                                                  Memory
                     Immature        Transitional      Naive mature     Unswitched  switched     Plasmablast
                                T1       T2       T3                     (MZ-like)
              IgM      ++       +++      ++       +        +               +        -                -
              IgD       -       +        ++       ++       ++              +        -                -
              R123     +        +        +        Int      -               +        +               +
              CD10     +        +        +/-      -/+      -               -        -               +/-
              CD19     +        +        +        +        +               +        +               lo
              CD24     +++      +++      ++       +        +               +        -                -
              CD27      -       -        -        -        -               +        +               hi
              CD38     +++      +++      ++       +        +               lo       lo              hi
                       FIG 7.2  B-Cell Subsets in Peripheral Blood. Peripheral blood B-cell subsets can be identified
                       by differential staining for immunoglobulin M (IgM), IgD, CD10, CD19, CD24, CD27, and CD38
                       and by the use of the rhodamine dye R123, which is extruded by the ABCB1 transporter expressed
                       in naïve, mature B cells and, to a lesser extent, T3 transitional B cells.  B cells that are CD20 +
                                                                                36
                                                                                                4
                           +
                                     −
                       CD27 CD43 CD70  are currently the best candidates for the human B-1-cell counterparts,  but
                                +
                       this is subject to change. In addition to these subsets found in blood, germinal center B cells
                                                                         −
                                                                                          +/−
                       found in the spleen, and lymph nodes are characterized as IgD CD38  CD10  CD27 ; marginal
                                                                              ++
                                                                                    +
                       zone (MZ) B cells are typically CD27 CD21 CD23 CD1c IgD ; and long-lived plasma cells found
                                                        ++
                                                   +
                                                              +/−
                                                                       −
                                                                    +
                                                                     −
                                                                +
                       in bone marrow, the spleen, and tonsils are CD138 CD20 CD38 .
                                                                          ++
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