Antibody maturation

The previous sections described structural studies of antibody maturation as a method to understand the evolution of binding (and catalysis) in the immune system. The technique of directed evolution parallels the process of affinity maturation. Both methods use random mutagenesis and gene shuffling, followed by screening and/or selection to identify mutants with the desired function. In contrast to affinity maturation,... 

Jackson JR, Sathe G, Rosenberg M, Sweet R, In vitro antibody maturation. Improvement of a high affinity, neutralizing antibody against IL-1 beta, J. Immunol., 154 3310-3319, 1995. 

These are supplied by the secretion of peptide molecules (termed cytokines or lymphokines) fiom a subset of the T-cell family (the helper T cells, TH cells). These peptide molecules (interleukins (IL) 2,4,5 and 6) stimulate the B cells to proliferate, undergo clonal expansion and mature into plasma cells which secrete antibody and also into the longer-hving, non-dividing memory cells. 

Subsequent antigenic stimulation results in high antibody titres (secondary or memory resporrse) as there is now an expanded clone of cells with memory of the original antigen available to proliferate into mature plasma cells (Fig. 14.1). 

A wide selection of monoclonal and polyclonal anti-Ca -ATPase antibodies have become available in recent years. Studies with these antibodies defined the localization of Ca " -ATPase in the sarcoplasmic reticulum of developing and mature skeletal muscles [60,262-270] and established a pattern of cross reactivity with various Ca -ATPase isoenzymes in the sarco(endo)plasmic reticulum [270-286] and in the plasma membrane [284,287-290] of skeletal, cardiac and smooth muscles. Antibodies have also proved useful in the quantitation of Ca -ATPase, both in muscles of diverse fiber types [291-294] and in COS-1 cells transfected with Ca -ATPase cDNA [97,103,126,127,129,215],... 

Plasma cell A lymphocyte that is a mature antibody-secreting B cell. 

Daugherty, P.S., Chen, G., Iverson, B.L. and Georgiou, G. (2000) Quantitative analysis of the effect of the mutation frequency on the affinity maturation of single chainFv antibodies. Proceedings of the National Academy of Sciences of the United States of America, 97, 2029-2034. 

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