B-Ly1 cells: immortal Ly-1+ B lymphocyte cell lines spontaneously arising in murine splenic cultures

Abstract

We have surveyed the molecular and functional properties of B-Ly1 cells, spontaneously occurring Ly-1+ cell tissue cultures lines established from murine spleen. Several features are surprising when compared to the conventional understanding of B cell physiology: In contrast to the major B cell subpopulation, these cells establish stable in vitro lines in the absence of nominal growth factors. This outgrowth is consistently accompanied by c-myc amplification and deregulation, and resistance to the effects of an autoregulatory IgM species which normally curtails the growth of B cells. These properties may be relevant to the disproportionate occurrence of Ly-1+ B cell malignancies in vivo. B-Ly1 cell lines consistently delete immunoglobulin constant region genes, and uniformly express lambda light chains, a rare murine isotype. These features may be causally related, and may reflect a novel recombinational activity (see this volume). Immunoglobulin expression can be modulated by conventional stimuli. However, the response is transient, and includes production of mature heavy chain isotypes ("class switching") without apparent switch deletion. Moreover, unstimulated B-Ly1 cells show transcriptional activity throughout the heavy chain locus, and a novel hypermutation activity affecting the immunoglobulin variable region. The mechanisms underlying this surprising pattern of immunoglobulin expression are unknown. However, one wonders whether this expression pattern, if common to Ly-1+ B cell in vivo, might provide modes to escape idiotypic or isotypic immunoregulation. If so, this may be relevant to the prevalence of autoantibody production by this subpopulation. Thus, we are hopeful that some of these unique properties, if confirmed in the Ly-1+ B cells in vivo, will provide more definitive markers for this subpopulation, and disclose mechanisms accounting for their distinctive physiology and pathophysiology.