B cells defects

Hyper-IgM syndrome can also arise if there is an intrinsic B cell defect that prevents B cells from switching to production of immunoglobulins other than IgM due to a mutation in the gene that codes for the mRNA-editing enzyme known as activation-induced cytidine deaminase (110). 

Primary immunodeficiencies are uncommon, and may occur in 1 in 10,000 individuals (6). Many primary immunodeficiencies are hereditary and congenital, and first appear in infants and children. Primary immunodeficiencies are classified into four main groups (7) relating to the lymphocytes (B-cells, T-cells, or both), phagocytes, or the complement cascade (8). Primary deficiency diseases result from B-cell defects in 50% of cases, from T-cell defects in ca 10%, and from combined B- and T-cell defects in ca 20%. Phagocytic disorders account for 18% and complement defects occur in 2% of all cases. 

Viable, fertile, decreased mature B cells defective B cell and mast cell function defective Fcgamma receptor signaling, therefore, loss of collagen induced platelet aggregation (Wang et al. 2000). 

The first indication that in some systems B cell defects may explain nonresponder status was obtained by Shearer, Mozes and Sela in studies of the transfer of limited number of bone marrow cells and thymocj es to irradiated recipients to reconstitute their responses. Using this approach, they found that the defect in the response of SJL mice to (Phe,G)-A- -L could be attributed to both thymocytes and bone marrow cells, whereas with the antigen (Phe,G)-Pro- -L, the defect in SJL and DBA/1 mice was located only in bone marrow cells. ... 

The non-responder phenotype may result from a T cell defect, from a B cell defect or from defects in both cell types. 

Patients with T cell deficiency have much more serious susceptibility to infection than patients with complete or partial B cell defects. In its most severe forms, T cell deficiency results in an inability to terminate opportunistic infections with organisms that are ordinarily innocuous. Consequently, varicella, vaccinia, and herpes and measles viruses can be fatal infections. The enterobacilli are commonly invasive in patients with T cell defects and infection with Monilia is almost universal. Malignancy of both the lymphoreticular organs and other viscera is also a common complication of the T cell disorders. 

Nagasaw, T., Hirota, S., Tachibana, K., Takakura, N., Nishikawa, S., Kitamura, Y., Yoshida, N., Kikutani, H., and Kishimoto T. (1996). Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382 635-638. 

Nagasawa T, Hirota S, Tachibana K, et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 1996 382 635-8. 

G4. Giblett, E. R., Ammann, A. J., Wara, D. W., Sandman, R., and Diamond, L. K., Nucleoside phos-phorylase deficiency in a child with severely defective T cell immunity and normal B cell immunity. Lancet 1, 1010-1013 (1975). 

AlQaoud, KM., Fleischer, B. and Hoerauf, A. (1998) The Xid defect imparts susceptibility to experimental murine filariasis - association with a lack of antibody and IL-10 production by B cells in response to phosphorylcholine. International Immunology 10, 17—25. 

Deldar, A., Lewis, H.B., Bloom, J.C., Apostoli, A. and Weiss, L. (1985). Residual stem cell defects associated with cephalosporin therapy in dogs. Blood 66 1202. 

Meissner, M., Reichert, T. E., Kunkel, M., Gooding, W., Whiteside, T. L., Ferrone, S., and Seliger, B., 2005, Defects in the human leukoc34e antigen class I antigen processing machinery in head and neck squamous cell carcinoma association with clinical outcome, Clin. Cancer Res. 11 2552-2560. 

A similar phenomenon has also been reported in B cells derived from chronic lymphoid leukemia (CLL) patients in which mFas is deficient or defective. Fresh de novo CLL cells, which express low levels of mFas, are resistant to agonistic anti-Fas mAb-mediated apoptosis, while CLL cells that acquire abundant mFas after short-term culture become sensitive (T4) to such induction of apoptosis. This flexibility in production of the isoforms is expected to provide a target for selective molecular therapy of tumors on the basis of manipulating decoy action of sFas. 

Finally, in this brief overview of lymphocyte defects, mention should be made of mutations affecting major histocompatibility-complex (MHC) Class II molecules. These mutations affect a multiprotein transcription factor complex that regulates the expression of MHC Class II molecules (121). Affected patients have undetectable levels of MHC Class II antigens HLA-DP, DQ, and DR on the surface of monocytes and B cells. Lack of these antigen-presenting molecules leads to impaired immune response. Affected individuals have moderate lymphopenia with a severely reduced number of CD4+ T cells and normal or increased numbers of CD8+ T cells. Since MHC molecules in the thymic epithelium play a key role in positive and negative selection of primitive T cells, selection of competent T cells is also affected in the absence of MHC Class II antigens. 

X-Linked hyper-IgM syndrome Defect in gene coding for CD 154 on activated T cell which interacts with receptor on B cells (CD40). B cells make only IgM. Defect also due to mutation affecting switching of IgM to other immunoglobulins. 

X-Linked agammaglobulinemia Defect in gene coding for Bruton tyrosine kinase responsible for B cell growth and maturation. 

Conley, M. E., Larche, M., Bonagura, V. R., etal. Hyper IgM syndrome associated with defective CD40-mediated B cell activation. J. Clin. Irxvest. 94, 1404-1409 (1994). 

FIGURE 5.27 (a) The fluorite structure of UO2 with a unit cell marked in bold, (b) Interstitial defect cluster in U02+jf. Uranium positions... 

Figure 10.3. Schematic representation of monoclonal antibody production using immortalized hybrid cells that secrete antibodies selective for the target antigen. The mortal, immune B cells Isolated from mice immunized with a target antigen are fused with myeloma, immortal B cells that express defective antibodies. The selecting of antigen-specific, immortal hybrid cells (hybridomas) results in identification of unique clones of cells that express antibodies with high specificity and affinity (monoclonal antibodies). These cells are cloned and expanded for large-scale monoclonal antibody preparations.

Figure 5.12 (a) Ordered defects in monoclinic TiOfTij gOj g) (b) ordered defects in (orthorhombic) nonstoichiometric TiOj l (c) coherent intergrowth of (a) and (b) along the (120) planes of rocksalt structure. Lines indicate unit cell faces of the superstructures. (After Anderson, 1984.)... 

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