Expression of V-region-like determinants on Ig-negative precursors in murine fetal liver and bone marrow

Abstract

IDIOTYPES, as defined by Oudin¹, are antigenic markers associated with antibodies produced by a single individual. The demonstration of ‘individual antigenic determinants’ on human myeloma proteins² introduced the concept of idiotype as a clonal marker of Igs. However, as the operational definition of an idiotype is based on the specificity of anti-idiotype antisera, the extent of cross-reactivity of a particular idiotype, and therefore the definition of idiotype, depends on the criteria set for the preparation of reagents. In fact, a number of ‘public’ or ‘cross-reactive’ idiotypes are currently described which are produced by all individuals of a strain or species or even by different species³. Yet, idiotypes are exclusively considered as markers of V-gene products defining groups of related Ig molecules. The basic concept of Jerne's network theory⁴, however, postulates that the universes of idiotypes and of antigens are identical. As a consequence, the finding of idiotype-cross-reactive determinants on non-Ig molecules should be the rule. We have observed⁵ that a class of polyclonally distributed mitogen receptors on splenic B cells bear determinants cross-reactive with the public idiotype of the J558 myeloma protein of BALB/c origin. We have investigated the possibility that this finding might be related to the mechanism of generation and regulation of the antibody repertoire. Having no indications on the growth regulation of B-cell precursors, we started to investigate the antigenic relationship between Ig idiotypes and mitogen receptors on those cells. We report here the cross-reactivity between several germ-line idiotypes and non-Ig surface structures expressed on cells present in haematopoietic tissues. We hypothesise that growth receptors on precursor B cells have determinants cross-reactive with germ-line V-gene products, and that precursor cells are driven and selected by interactions between these receptors and molecules with anti-idiotype specificity also belonging to an incipient network transmitted in the germline.