Heavy chains , human

In this chapter we will discuss immunoglobulins of the IgG class, which is the major type of immunoglobulin in normal human serum, and which has the simplest structure. Each chain of an IgG molecule is divided into domains of about 110 amino acid residues. The light chains have two such domains, and the heavy chains have four. 

Bertran, J., et al. Stimulation of system y(+)-like amino acid transport by the heavy chain of human 4F2 surface antigen in Xenopus laevis oocytes. Proc. Natl. Acad. Sci. U. S. A. 1992, 89, 5606-5610. 

Similar results were recently obtained with a human monoclonal antibody, with KDEL sequences fused to the C-termini of both heavy chains, expressed in tobacco [33]. As observed for the invertase-HDEL fusion, about 90% of the N-linked glycans on this antibody were of the high-mannose type, with 6-9 mannose residues, while a fraction contained the immunogenic P(l,2)-xylose glyco-epitope (Fig. 15.6). However, this antibody was not a(l,3)-fucosylated, a glycan modification occurring in the trans Golgi [34]. 

Fusion of human lymphocytes with human lymphoblastoid cell lines is a very inefficient process. Fusion of human lymphocytes with murine myeloma cells lead to very unstable hybrids. Upon fusion, preferential loss of human genetic elements is often observed. Unfortunately, particularly common is the loss of chromosomes 2,14 and 22, which encode antibody light and heavy chain loci. The production yields of human monoclonals upon immortalization of the human B-lymphocyte (by whatever means) are also low. 

Mature B lymphocytes express AhR and ARNT,10,12 and the ability of TCDD to suppress primary antibody responses has been known for a long time (reviewed in4). While the precise mechanisms resulting in suppression of T-dependent B cell responses in vivo have not been fully elucidated, it is clear that direct effects of TCDD on B cells plays a role. Studies using two B cell lines with differential AhR expression have linked suppression of LPS-induced IgM production to AhR activation, and have shown that AhR interactions within the 3 alpha immunoglobulin heavy chain enhancer directly influence antibody production.52-54 TCDD also appears to directly modulate the expression of CD19 on human B cells, suggesting another mechanism by which TCDD down-modulates the responsiveness of mature B cells.55... 

Cassatella, M. A., Hartman, L., Perussia, B., Trinchieri, G. (1989). Tumor necrosis factor and immune interferon synergistically induce cytochrome b.245 heavy-chain gene expression and nicotinamide-adenine dinucleotide phosphate hydrogenase oxidase in human leukemic myeloid cells. J. Clin. Invest. 83,1570-9. 

Voluntary muscles contain a variety of fibre types which are specialized for particular tasks. Most muscles contain a mixture of fibre types although one type may predominate. All human skeletal muscles are composed of several different muscle fibre types. Up to seven different fibre types have been identified histochemically based on the pH stability of myofibrillar adenosine triphosphatase and on the myosin heavy chain profile. Innumerable fibre type transients exist due to continuing adaptation processes. However, three main... 

Lefranc, M. R, Hammarstrom, L., Smith, C. I. E., and Lefranc, G., Gene deletions in the human immunoglobulin heavy chain constant region locus Molecular and immunological analysis. Immunol. Rev. 2, 265-281 (1991). 

Infliximab is a chimeric monoclonal antibody targeted against TNF-a. It consists of a human IgGi Fc heavy chain and partial K-Iight chain fused to a murine hypervariable region. Infliximab binds to both soluble and transmembrane forms of TNF-a and inhibits their ability to bind to TNF receptors. It does not inhibit TNF- 3, which binds to the same receptors as TNF-a. Infliximab is administered intravenously, usually at 4- to 8-week intervals. 

Structures of TNF-K antagonists used in rheumatoid arthritis. CH, constant heavy chain CL, constant light chain Fc, complex immunoglobulin region VH, variable heavy chain VL, variable light chain. Red regions, human derived blue regions, mouse derived. 

Dersimonian, H., Schwartz, R.S., Barrett, K.J., et al. (1987). Relationship of human variable region heavy chain germline genes to genes encoding anti-DNA autoantibodies. J. Immunol., 139, 2496-2501. 

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