B cell clones

Monoclonal antibodies are derived from a single, monospecific B cell clone. Monoclonal antibodies can be obtained from hybridoma cells that result from the fusion of antibody-producing B cells with immortal cells of a myeloma cell line. 

The decision regarding whether to use a polyclonal antibody or monoclonal antibody depends on a number of factors, the most important of which are its intended use and whether the antibody is readily available from commercial suppliers or researchers. The concentration and purity levels of specific antibody are higher in monoclonal antibodies. However, polyclonal antibodies are known to have a higher affinity and a better specificity than monoclonal antibodies, because they are produced by a large number of B cell clones each generating antibodies to a specific epitope, and because polyclonal sera are a composite of antibodies with unique specificities (Lipman et al. 2005). 

The 15-kDa J chain is synthesised by the same B-cell clone that produces the IgA molecule. The IgA molecules are transported across the epithelial cells and enter the lumen, this transport being mediated via another protein called the secretory chain (SC). The IgA molecules that are finally secreted are dimers of relative molecular mass of 400 kDa. The heavily glycosylated SC (80 kDa), synthesised and secreted by the epithelial cells, binds to the IgA molecules via non-covalent bonds. The IgA molecule thus has a valency of 4 (i.e. a single molecule has four antigen-binding sites), with all four sites recognising the same antigen. 

Somatic mutation. During differentiation of B cells into plasma cells, the coding genes mutate. In this way, the primordial germline genes can become different somatic genes in the individual B cell clones. 

An immunogen induces antibodies from many B cell clones, producing a polyclonal antibody response. In contrast, the propagation of an isolated B cell clone produces an antibody of single specificity. However, the problem is that in tissue culture medium, B cells die within a few days of their isolation from, for example, a mouse spleen. To circumvent this problem, immortality can be conferred on B cells by means of viral transformation Epstein-Barr virus can be used. Alternatively, fusion to cancerous cells is carried out to generate hybrids or hybridomas. Generally, the former procedure is used to immortalize peripheral blood B cells and produce human monoclonal antibodies, while myeloma cells are used to produce murine monoclonal antibodies. 

A single individual may produce a population of antibody specificities, an antibody repertoire, which is a reflection of all the B cell clones (lymphocyte repertoire) capable of immunoglobulin (Ig) synthesis and secretion in response to antigenic stimulation, but also in absence of exposure to environmental pathogens [48, 49]. Natural antibodies, in fact, are germ line-encoded molecules produced by a distinct population of peritoneal B cells, bearing the cell surface marker CD 5 and are present in the sera and interstitial fluids of healthy individuals [49-51]. 

Normal B cells are incapable of extended growth outside the animal. The production of monoclonal antibodies, however, involves establishment of a B cell clone producing the antibody in long-term culture. This is accomplished by immortalizing the B cell using a transforming virus such as the Epstein-Barr virus... 

The efficacy of polysaccharide vaccine in preventing invasive pnenmococcal disease, pnenmonia, and death has been assessed in a donble-blind, randomized, placebo-controlled trial in 1392 HIVl-infected adnlts in Uganda (14). The vaccine was well tolerated. However, it was ineffective and is not recommended for nse in HIVl-infected indivi-dnals. Reassessment of recommendations for polysaccharide vaccine immunization may be necessary in some countries. The authors suggested that the vaccine causes destruction of polysaccharide-responsive B cell clones. 

Icard Ph, Pelletier L, Vial M-C, et al. 1993. Evidence for a role of antilaminin-producing B cell clones that escape tolerance in the patholgenesis of HgCl2-induced membranous. Nephrol Dial Transplant 8 122-127. 

Since autoantibodies are detectable in healthy subjects it is not possible to say whether or not their increased detection in CNS degenerative and inflammatory disease is a result of a new primary response or the stimulation of preexisting B-cell clones by the macrophage transfer of antigen from the brain. In a chronic inflammatory disease with a suspected autoimmune aetiology such as multiple sclerosis there has been a failure to identify a primary pathogenic autoantigen, but many... 

The initial discovery and description of the constant, variable, and hypervariable domains and elucidation of the primary structures of the immunoglobulins was made possible because of the disease multiple myeloma. In multiple myeloma, a single B-cell clone (mono-clone) synthesizes large quantities of structurally identical or monoclonal antibody molecules. Isolation of immunoglobulin from multiple myeloma patients who were producing structurally different immunoglobulins... 

Because each B-cell clone produces antibody to a single epitope on an antigen, an opportunity exists for producing chemically and functionally homogeneous antibody in substantial quantity. However, the short B-cell lifetime that is determined by normal apoptosis initially made this impractical. However, the discovery by Kohler and Milstein that B cells could be fused with immortal myeloma cells to create hybridomas that can be maintained almost indef-... 

Also see color figure.) B-cell clonal selection. Antigen binding to the surface Ig (monomeric IgM and IgD) receptors occurs only to the B-cell clone that recognizes a particular epitope on the antigen (Figure 35-1). 

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