Ly-1 B cells: functionally distinct lymphocytes that secrete IgM autoantibodies.

Abstract

Studies presented here introduce another perspective on the mechanisms responsible for IgM autoantibody production. A unique subpopulation of B lymphocytes (Ly-1 B) that concomitantly expresses IgM, IgD, Ia, and Ly-1 membrane glycoproteins is present at higher frequencies in NZB and NZB-related mice. The Ly-1 B subpopulation in these autoimmune dinials is responsible for the "spontaneous" IgM secretion demonstrated with cultured JNZB spleen cells and contains the cells that secrete typical NZB IgM autoantibodies to single-stranded DNA and to thymocytes. In addition, the Ly-1 B population in normal mouse strains (and in NZB) contains virtually all of the spleen cells that secrete IgM autoantibodies reactive with bromelain-treated mouse erythrocytes. Since a different B-cell subpopulation (IgM+, Ig-, Ly-lE) (11). This Ly-1 B subpopulation (11, 12), which is also marked by characteristic levels of surface IgM and IgD, is present at increased frequencies in NZB and NZB-related autoimmune mice (e.g., 5-10% in NZB spleen compared with 1-2% in BALB/c spleen). Furthermore, it tends to be more active in NZB in the sense that Ly-1 B cells sorted from these animals spontaneously secrete much more IgM in vitro than BALB/c Ly-1 B cells sorted and cultured at the same density (11).Continuing these studies, we present evidence here defining the role that Ly-1 B cells play in autoimmunity. We show (i) that FACS-sorted Ly-1 B cells from LPS-stimulated BALB/c mice are responsible for essentially all of the IgM autoantibody produced to bromelain-treated mouse erythrocytes; (ii) that the spontaneously secreted IgM from FACSsorted NZB Ly-1 B cells contains typical NZB autoantibodies reactive with DNA and with thymocyte cell surface antigen(s); and (iii) that although Ly-1 B cells produce most of the IgM autoantibodies produced to the above antigens, they produce only minimal IgM responses to exogenous antigens such as sheep erythrocytes, 2,4,6-trinitrophenyl-conjugated keyhole limpet hemocyanin (TNP-KLH), and TNP-Ficoll.Finally, to complete the identification of Ly-1 B cells as a functionally unique subpopulation, we show that the IgM antibodies produced to exogenous antigens are mainly produced by cells whose surface marker characteristics (IgM', IgD-, Ly-l-)

Class switching and consecutive loss of dsDNA‐reactive B1a B cells from the peritoneal cavity during murine lupus development

“…The enrichment of autoreactive specificities in the B1a B cell compartment [8][9][10][11][12], their low activation threshold and the increased numbers of B1 B cells in various murine lupus models [4,6] have led to the speculation of involvement of these cells in the pathogenesis of autoimmunity. This assumption is supported by studies showing amelioration of murine lupus when B1 B cells were either genetically or physically depleted [16,17].…”

“…Besides the PC they can be detected in the spleens, blood and inflamed target organs [7]. Human and murine B1a B cells are enriched for autoreactive specificities targeting DNA, thymocytes, immunoglobulins and phosphatidylserine [8][9][10][11][12]. B1 cells have additionally been shown to be the source of anti-erythrocyte antibodies in a transgenic model of autoimmune hemolytic anemia [13].…”

B cells expressing cd5 are increased in sjögren's syndrome

“…The proliferating cell in CLL is a CD5+ B cell, which may produce monoclonal IgM-RF sharing a cross-reactive idiotype with RF produced by patients with SS (13,14). Genetically susceptible autoimmune strains of mice also manifest increased numbers of CD5+ B -PHA cells (termed Ly-l), which produce autoantibodies such as anti-erythrocyte and anti-DNA (15). Aged autoimmune mice develop clonal proliferation of Ly-l+ B cells that may be analogous to the B cell lymphomas that arise in humans with primary SS (16,17).…”

“…Studies in mice demonstrated that a cell analogous to the human CD5-t B cell and expressing cell surface Ly-1 is increased in number in autoimmune mice and becomes clonal in aged mice (15)(16)(17). Recent studies in normal mice suggest that these unusual B cells may have regulatory properties and helper function (18).…”

The Unique Antigen Receptor Signaling Phenotype of B-1 Cells Is Influenced by Locale but Induced by Antigen

“…This is marked by a diminished ability for intracellular Ca 2ϩ mobilization, aberrant proliferation, and increased apoptosis after BCR cross-linking (6,7,9,10). While B-1 cells only comprise a small percentage of all B cells, they are the primary source of the serum Ab in unimmunized mice, known as natural Ab (3,11,12). The majority of natural Ab is low affinity and polyreactive, with the ability to recognize autoantigens as well as those from bacterial and parasitic sources.…”