3.1.4.2 Intensity of tonic signal and differentiation of lymphoid follicular B-cells or MZ B-cells


antigen–antibody complexes as well as in the selection of memory B-cells during GC reactions (GCRs) [33]. They contain naive B-cells, and adjacent to which are T-cell zones that form the periarteriolar lymphoid sheath (PALS). Phenotypically, they are IgM+/-IgD++, CD21+/, and CD23+, in mice.

4. B-cell markers: the main molecules of the B-lymphoid lineage

Introductory Chapter: B-Cells

DOI: http://dx.doi.org/10.5772/intechopen.90636

the bone marrow), which is capable of transducing extremely potent B-cell

activation signals. Mutations in the gene coding for CD40 ligand (CD40L/CD154), predominantly expressed by activated CD4+ T-cells, lead to X-linked hyper-IgM syndrome (HIGM1), a severe primary immune deficiency (PID) in humans, characterized by recurrent infections, associated with very low or absent IgG, IgA, and IgE levels, but normal or elevated serum levels of IgM [47]. B-cells can also be identified using the inhibitory co-receptor CD72 (Lyb-2 in mice), containing an ITIM in the cytoplasmic. CD72 specifically recognizes the RNA-containing

endogenous TLR7 ligand Sm/ribonucleoprotein (RNP) by C-type lectin-like domain (CTLD) located in its extracellular region and specifically inhibits B-cell responses to Sm/RNP by recruiting SH2 domain-containing phosphatase 1 (SHP-1) to the

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The majority of human peripheral blood B-cells express on their surface IgM and IgD that have the same antigenic specificity. In addition, in humans, a large population of circulating cells expresses membrane lgG or IgA (but very little IgE). In some tissues, including intestinal mucosa, B-cells selectively express membrane IgA. In addition to the Igα/Igβ heterodimer marker, which is part of the BCR complex, there are also other molecules on the B-cell surface that play notable roles in various cellular functions, especially in B-cell regulation, such as human complement receptor type 2 (CR2, C3d), designed as CD21, that regulates B-cell proliferative responses, and serving as a receptor for the C3d, C3dg, and iC3b proteins of complement. B-cells also express receptor for complement component C3b (CR1, CD35) as well as for Fc fragments (FcR) of certain Ig isotypes, such as IgG (FcγRII-B1, CD32). Of note, only FcγRIIB1 and FcγRIIB2 have an immunoreceptor tyrosinebased inhibitory motif (ITIM) sequence among the FcγR receptor family and are therefore inhibitory FcRs; they do not induce phagocytosis and represent an important receptor-mediated feedback circuit regulator by circulating antigenspecific IgG [24, 37]. CR2/CD21 has also been described as a receptor for the envelope glycoprotein gp350/220 of the Epstein–Barr virus (EBV) [38]. Other molecules are frequently used in routine practice as primary markers for identifying human B-cells, including CD19, CD20, and CD22 markers. CD19 is expressed at all stages of B-cell lineage, including normal plasma cells. CD20, a molecule restricted to the B-cell population, has been shown to be implicated to form calcium channels in cell membrane [39], and as an effective target for immunotherapy in treatment of B-cell lymphoma, as well as in a number of autoimmune diseases, such as type 1 diabetes [40]. It occurs at the early pre-B-cell stage of development and remains throughout all stages of B-cell maturation [41], ranging from pre-B-cells in the bone marrow to short-lived plasmablasts [42]. CD22, a B-cell-restricted surface molecule that regulates BCR signaling in mature B-cells [43], is an early marker and persists at all stages of B-cell differentiation, which has allowed it to be a useful pan marker for all mature B-cell subsets [44]. Recognized as a B-cell-specific sialic acid binding Ig-like lectin 2 (Siglec-2; B-lymphocyte cell adhesion molecule [BL-CAM]), CD22 has been exploited as a therapeutic target for humanized anti-CD22 monoclonal antibody to treat B-cell leukemia [45]. Both immature and mature mouse B-cells as well as subsets of T-cells and NK cells and subset of abnormal T-cells involved in the pathogenesis of systemic autoimmunity in MRL-Faslpr and MRL-Fasgld mice express one of the five isoforms of the transmembrane tyrosine phosphatase CD45 (LCA) found on lymphocytes [46], i.e., CD45R (B220, CD45RABC), which has been known to play a major role in lymphocyte signaling and activation. Other B-cell surface molecules allow them to cooperate with T-cells. They include essentially MHC II antigens (DR, DP, and DQ, in humans, and IA and IE, in mice) and CD40 (a member of the TNF receptor superfamily, also expressed on B-cell precursors in
