Lymphocyte Repertoire

Phyllis-Jean Linton, Department of Immunology, The Scripps Research Institute, California, USA

Over the years two experimental approaches have been used to assess antigen-specific B cell populations at the clonal level. These use antigenic or polyclonal mitogenic stimulation of B cells in limiting dilution. Since polyclonal stimulation encompasses a broad range of B cell responsiveness, assays for antibody production discriminate between the various antigen reactivities. In contrast, antigen stimulation is more selective in the B cells that respond, thus enabling analyses for positive antibody production. The advent of hybridoma technology not only allowed for ease in experimental execution but also made feasible the analyses of the molecular events involved. With advances in molecular biology technology, e.g. polymerase chain reaction (PCR) and reverse transcriptase-PCR, sequences could be obtained from single cells without any form of selection.

Among the early major findings are that B cell antigen receptors are clonally distributed, each B cell expresses a single immunoglobulin specificity and each stimulated primary B cell gives rise to a clone of antibody-forming cells (AFCs) whose antibody replicates the variable region clonotype of the antigen receptor of the original stimulated B cell. Although the primary B cell clonotype repertoire is extremely diverse, individuals of the same murine strain tend to express similar repertoires. Many studies have led to the conclusion that the B cell clonotype repertoire of a given mouse strain as well as the individual mice is highly restricted during late fetal and early neonatal development, and is acquired in a highly patterned and reproducible fashion. Among the more recent findings are the elucidation of the molecular events involved in the diversity of B cell repertoire expression, the mechanisms by which each B cell obtains a single specificity, and the mechanisms that underlie the gradual acquisition of B cell repertoire during neonatal development.

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