Nolan H. Sigal

The B-Cell Clonotype Repertoire

Publisher Summary Implicit in the clonal selection hypothesis is the existence of a repertoire of genetically determined B-cell clonotypes. This chapter focuses on the genetic determination, the development, and the regulation of this library of immunologic responses. The authors draw on their extensive experience in this field to put into perspective the clonal selection scheme with its more than 107 clonotypes and multiple forms and levels of control. In keeping with the genetic basis of the scheme, all members of an inbred strain express the same repertoire of major clonotypes. The maturation of the repertoire from its restricted state in the neonate to its full development in the adult is presented, and the many levels for control of this expression are discussed. The neonatal B cell repertoire is significantly more restricted and, preliminarily, appears repetitive within a strain. Clonotype expression is controlled at many levels and many assumed polymorphisms in variable-region structural genes between strains are more closely reflect disparities in control of clonotype expression.

The interplay of evolution and environment in B-cell diversification.

Experiments were conducted to show that addition of dimethyl sulfoxide (DMSO) to A-muLV-transformed tissue-culture cells stimulates their differentiation and results in the production of immunoglobulins. The Ig M molecules are eventually deposited on the cell surface. The induced state of differentiation may be either that of the small B lymphocyte which synthesizes and inserts monomeric Ig M into the cell membrane but does not secrete it, or that of a precursor to the small resting B cell which synthesizes monomeric Ig M and probably also inserts it into the surface membrane. (HLW)