Analysis of the Murine Antibody Repertoire

Duke University, Durham NC

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Abstract

.o. The murine antibody repertoire experiences a series of expansions and contractions that coincide with specific stages of B-cell development arid differentiation. The initial repertoire of antibody specificities generated by V(D)J recombination is reduced during B-cell maturation by the effects of immunological tolerance mechanism acting on immature and transitional B cells. The purging of autoreactivity from developmentally immature B cell compartments it is thought to be accomplished by at least three mechanisms: cional deletion by apoptosis, inactivation by energy, and receptor editing, the induction of secondary V(D)J gene rearrangements to replace self- reactive receptors. Receptor editing is believed to be the premiere mechanism for B-cell tolerance. Questions remain, however, regarding how the process of receptor editing acts and whether experimental evidence for receptor editing reflects the induction of genetic changes in autoimmune B cells or selection for variants that spontaneously undergo secondary rearrangements. We shall investigate the tolerizing contractions of the B-cell repertoire with particular reference to: 1) the signals and developmental stages of B cells that initiatelsupport receptor editing;2) the role of self-antigens in the induction of regulated RAG 1/2 expression and rearrangement, and;3) the selection criteria that might determine clonal tolerance/selection during B-cell maturation in viva. Qom cap mop axiom 0-c 0opccc woo'- t00 0co -td