Overall, early B cell development is similar in humans and mice (Burrows and Cooper, 1997). Defined by the rearrangement of the immunoglobulin (Ig) genes, a hematopoietic stem cell in bone marrow undergoes the early pro-B cell stage, late pro-B cell stage, pre-B cell stage, and finally becomes an immature B cell (Burrows and Cooper, 1997). The most striking difference occurs at the molecular level in the signaling control of the pre-B cell receptor (pre-BCR) stage (Conley et al., 2000). For example, more than 75% of the human genetic disorders in B cell development are due to the mutation in Bruton's tyrosine kinase (Btk) (Conley et al., 1998) with clinical manifestations such as repeated bacterial infections, hypogammaglobulinemia, and less than 1% of normal B-cell numbers in the periphery. Molecular research of this disease, named X-linked agammaglobulinemia (XLA) (Campana et al., 1990) is characterized by the inability to produce immunoglobulins (Igs) of all isotypes. In contrast, the mouse model of Btk mutation, Xid mouse (X-linked immunodeficiency) is still semi-competent in antibody (Ab) production and has almost half the normal B cell numbers and only low concentrations of IgM and IgG3 (Wicker and Scher, 1986). This difference appears to be due to the observation that Btk in humans controls B cell development at the point of transition from pro-B cell to pre-B cell (Campana et al., 1990), whereas in mice it seems that Btk plays a role only after the immature B cell stage is reached (Kerner et al., 1995). Interleukins (IL) -2, IL-4, IL-7, IL-9, and IL-15 receptors share a common signal transducing chain—yc (Cao et al., 1995). Mutation in the yc chain blocks both T and B cell development in mice. In contrast, patients with X-linked severe combined immunodeficiency (XSCID) disease caused by a yc mutation have normal B cell development and are deficient in T cell development (Cao et al., 1995). Thus, humans and mice show a different requirement for IL-7 in B cell differentiation (Prieyl and LeBien, 1996).

Mature B cells are heterogeneous, and distinct B cell populations have unique receptor expression profiles and functional repertoire. For example, the CD5 receptor, an antigen (Ag) receptor adaptor protein, is critical in the regulation of autoimmunity in B-1 cells (Hayakawa and Hardy, 2000). Studies in humans suggested that

(1) CD5 and CD23 are exclusively expressed on murine B cells, whereas co-expression of CD5 and CD23 on human cord blood B cells is normal (Gagro et al., 2000);

(2) in humans, CD5+ and CD5~ B cells have an indistinguishable response to in vivo/in vitro stimulation in regard to the expressional change of CD5 and CD23 (Gagro et al., 2000); and (3) CD40, together with BCR co-stimulation, can increase CD5 expression and at the same time down-regulate CD23 expression in humans. However, in mice, CD40 will decrease CD5 expression but enhance CD23 expression, and surface IgM cross-linking can induce the CD5 expression (Gagro et al., 2000; Wortis et al., 1995). The plasma cell is the terminal differentiation stage in B cell development. One of the characteristics of human plasma cells is high CD38 receptor expression. Lower levels of CD38 are also found on B cells located in germinal centers so CD38 expression is used as marker of B cell activation and differentiation (Mainou-Fowler et al., 2004). This criterion is not applicable to the mouse model since CD38 expression remains high until the B cell is activated and moves into the germinal center where CD38 expression is totally absent in plasma cells (Oliver et al., 1997). Humans and mice also differ in the isotypes of Abs produced (Haley, 2003). Most notably, rats do not produce IgA, and there are additional differences in the organization and regulation of IgG subclasses. Structurally, no homologues of human IgG subisotypes can be found in mouse or rat. Functionally, an important role of human IgG is opsonization, whereas in the rat IgG1 can mediate the uptake of pathogens by binding to complement, and mouse IgG1 is involved in hyper-sensitivity reactions (Haley, 2003).

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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