Normal mouse peritoneum contains a large population of Ly-1+ (CD5) B cells that recognize phosphatidyl choline. Relationship to cells that secrete hemolytic antibody specific for autologous erythrocytes.

Abstract

The most remarkable feature of the immune response is its ability to generate cells and antibodies specifically reactive with an enormous variety of foreign antigens while normally avoiding the production of autoreactive elements. An accumulating body of data demonstrates that a distinct lineage of B cells (1), the Ly-1 + B cell subset, does not display this feature, but rather is associated with the production ofautoreactive antibodies (2). We are unaware of autoimmune pathology directly demonstrated to be the result of an Ly-1 + B cell-Ig product; however, Ly-1+ B cell frequency is elevated in some autoimmune strains of mice (3). In addition to their association with autoreactive antibody, Ly-1 + B cells have been shown to have unique growth potential (1, 4); to produce most of the serum IgM found in normal, unimmunized animals (4); and the Ig repertoire of the subset may be restricted (4, 5). These findings imply that this subset has a role in normal physiology, and perhaps autoimmune pathology. A B cell subset has been identified in humans that bears the homologous marker Leu-1/T1 (CD5) (6). A similar functional role for CD5+ B cells in man has been proposed (7); human CD5+ B cells have been shown to produce autoreactive antibody (8, 9) and to be present at elevated frequency in rheumatoid arthritis (10).Normal mice produce antibodies that are reactive with protease-treated autologous erythrocytes (BrMRBC) 1 (11) ; cells producing such antibodies are present in unimmunized mice at very high frequencies, as first demonstrated by Cunningham (12) . We and others (13)(14)(15) have shown that at least some anti-BrMRBC plaqueforming cells (PFC) recognize the polar headgroup of the common membrane phospholipid, phosphatidyl choline (PtC). Most splenic anti-BrMRBC PFC have been

PD‐L2 expression extends beyond dendritic cells/macrophages to B1 cells enriched for VH11/VH12 and phosphatidylcholine binding

“…For four-color staining, biotin-labeled anti-PD-L2 and streptavidin-APC were used. PtC-bearing, fluorochrome-encapsulating liposomes [10] were the kind gift of Dr. S. H. Clarke (University of North Carolina, Chapel Hill, NC). Data were acquired using a FACSCalibur flow cytometer (BD Biosciences) with CellQuest software (BD Biosciences) and were analyzed using FlowJo software (TreeStar).…”

“…Reconstitution of anti-PtC IgM in sIgM-deficient mice substantially reduced the bacterial load in a cecal ligation and puncture model [5]. Thus, V H 11/V H 12-expressing B1 cells play an important role in immunity; considering that PtC-binding B1 cells recognize protease-treated autologous erythrocytes, they may play a role in hemolytic autoimmune dyscrasias as well [10,12].…”

“…B1 B cells are the major source of natural immunoglobulin in normal unimmunized mice, providing a vital front line defense against bacterial and viral infection [4][5][6][7][8]. This function is associated with a skewed repertoire containing autoreactive specificities, one manifestation of which is expression of phosphatidylcholine (PtC)-binding V H 11 and V H 12 by a substantial portion of peritoneal B1 cells in unimmunized mice [9][10][11]. PtC is the polar headgroup of common membrane phospholipids.…”

“…Reconstitution of anti-PtC IgM in sIgM-deficient mice substantially reduced the bacterial load in a cecal ligation and puncture model [5]. Thus, V H 11/V H 12-expressing B1 cells play an important role in immunity; considering that PtC-binding B1 cells recognize protease-treated autologous erythrocytes, they may play a role in hemolytic autoimmune dyscrasias as well [10,12].B cells, like T cells, express programmed death-1 (PD-1), engagement of which negatively regulates B cell activity in vitro [13]. Surface levels of PD-1 are upregulated by BCR stimulation and down-regulated by …”

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

“…One highly represented example is the specificity encoded by germline V H 11 and V 9 Ig genes. This rearrangement is expressed by 5-15% of the peritoneal B-1 cells in normal mice and reacts with phosphatidylcholine (PtC), a normal component of the cell membrane (24). We recently reported that B cells constrained by a V H 11V 9 Ig transgene generated CD5 ϩ , PtC-specific B cells in both the spleen and peritoneum (22).…”