In B lymphocytes

NF-xB, originally defined as the enhancer of kappa light-chain expression in B lymphocytes, is a hcterodimeric protein that can rapidly activate several genes associated with the inflammatory process (reviewed by Schreck et al., 1992). The DNA binding, nuclear form, of NF-xB is a heterodimer composed of one Rel-A (65 kD) and one p50 (50 kD) subunit. However, both subunits can form homodimers that also have DNA-binding activity. The inactive form of NF-xB in non-stimulated cells is localized to the cytoplasm of resting cells, and is bound to its inhibitor IxB. 

In B lymphocytes, coupling of the antigen receptors to Erk MAPkinase is protein tyrosine kinase (PTK)-dependent (Pao et al, 1997). Following ligation of the BCR (Fig. 19.2) the PTK, Lyn, tyrosine phosphorylates the immunoreceptor tyrosine-based activation motifs (ITAMs) on the accessory transducing molecules Ig-a and Ig-(3, leading to the recruitment... 

Deehan, M., Harnett, M. and Harnett, W. (1997) A filarial nematode secreted product differentially modulates expression and activation of protein kinase C isoforms in B lymphocytes. Journal of Immunology 159, 6105-6111. 

The production process (Box 13.1) entails initial immunization of a mouse with the antigen of interest. The mouse is subsequently sacrificed and its spleen removed. (The spleen is an organ enriched in B-lymphocytes. Because of the immunization process, a significant proportion of these lymphocytes are likely capable of producing antibodies recognizing specific epitopes on the antigen.)... 

Chacko GW, Tridandapani S, Damen, J.E., Liu L., Krystal G., and CoggeshaU, K.M., 1996, Negative signaling in B lymphocytes induces tyrosine phosphorylation ofthe 145-kDa isositol polyphosphate 5-phosphatase, SHIP. J Immunol 157 2234-2238. 

Adenosine deaminase (ADA) was the first therapeutic enzyme coupled to PEG with the aim of reducing clearance and thereby overcoming the short half-life of ADA. Patients deficient in ADA are unable to regulate purine metabolism. As a result purine metabolites (e.g., adenosine monophosphate) accumulate to cytotoxic levels in B-lymphocytes and lead to severe B-cell depletion that presents clinically as severe combined immunodeficiency syndrome (SCIDS). While intramuscular injection of unmodified ADA provides some relief, antibodies develop rapidly against the protein and prevent it from being useful as replacement therapy. Even in the absence of antibodies, unmodified ADA s plasma half-life is only a few minutes. 

Clark GC, Blank JA, Germolec DR, et al. 1991a. 2,3,7,8-Tetrachlorodibenzo-p-dioxin stimulation of tyrosine phosphorylation in B lymphocytes potential role in immunosuppression. Mol Pharmacol 39 495-501. 

Bubien, J. K., Zhou, L. J., Bell, P. D., Frizzell, R. A., and Tedder, T. F. (1993). Transfection of the CD20 cell surface molecule into ectopic cell types generates a Ca2+ conductance found constitutively in B lymphocytes./. Cell Biol. 121, 1121-1132. 

Type I, or immediate immune, response involves the body s production of immunoglobulin E (IgE) antibodies in lymphatic tissue that bind to the surface of mast cells and basophils and prime them for action. The antibodies are produced in B lymphocytes during the period of sensitization. Sensitization occurs as the result of exposure to appropriate antigens through the respiratory tract, dermally, or by exposure via the gastrointestinal tract. Subsequent cross-linking of the antibodies... 

Zeidler, R., Eissener, G., Meissner, P., Uebel, S., Tampe, R., Lazis, S., and Hammerschmidt, W. 1997. Down regulation of TAPI in B lymphocytes by cellular and Epstein-Barr virus-encoded interleukin-10. Blood 90, 2390-2397. 

The increase in phosphoinositide hydrolysis appears to occur during the G0 and early G[ phases of the cell cycle. Cells will not tolerate a sustained increase in intracellular Ca2+ and actively extrude the ion. Recent evidence in B lymphocytes, using calcium probes and image intensifies, shows that when surface immunoglobulin is crosslinked the rise of intracellular Ca2+ occurs in repeated short bursts [37]. 

The present discussion is mainly concerned with the humoral response. Although many cells participate in this response, the site of antibody production is in B lymphocytes which, in their mature form, are called plasma cells. Each plasma cell produces antibodies with a given specificity, and there are many identical copies, or clones, of this cell type, all making the same monoclonal antibody. Other lines of plasma cells produce antibodies that recognise the same antigen, but have different... 

Briefly suimnai ize the major steps in B lymphocyte development. 

Cellular immunity The decline in T lymphocytes resulting from a drop in the number of CD8+ suppressor cells points to pre-existing cellular immunity (increase in the quotient CD4+ CDS" ), as does a rise in B lymphocytes (with an increase in T l)miphocytes in the portal fields) an inhibition of leucocyte migration was likewise found. D.H. Adams et al. (1991) identified an elevated expression of the ICAM 1 on the bile-duct epithelia. 

Abetimus is a selective immunomodulator for the treatment of systemic lupus erythematosus. It induces tolerance in B lymphocytes directed against double-stranded DNA by cross-linking surface antibodies. It also reduces serum double-stranded DNA antibodies and splenic double-stranded DNA antibody-producing cells in BXSB mice, giving improved renal function and histopathology, as well as prolonged survival (1). 

Those cytokines which are responsible for the specificity of the isotype switch event in B lymphocytes. They include IL-4 and TGF/3, and have in common the ability to induce the transcription of an immature (germline) form of RNA encoding the heavy chain isotype to which switching will be induced. 

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