The Bw Cells, a Novel B Cell Population Conserved in the Whole Genus Mus

Abstract

In common laboratory mouse strains, which are derived from the crossing between three subspecies, peritoneal B cells are enriched in B-1a cells characterized by the CD5+Mac-1+B220lowIgMhighIgDlowCD43+CD9+ phenotype. Intriguingly in other vertebrates, CD5+Mac-1+ cells have never been found in a specific anatomic site. To ascertain the peculiarity of the CD5+ peritoneal B cells in laboratory mice, we analyzed the peritoneal B cell subsets in 9 inbred and 39 outbred wild-derived mouse strains belonging to 13 different species/subspecies. We found that most of these strains do not have the CD5+ B-1a cell population. However, all of these strains including classical laboratory mouse strains, have variable proportions of a novel B cell population: Bw, which is characterized by a unique phenotype (CD5−Mac-1+B220highIgMhighIgDhighCD43−CD9−) and is not restricted to the peritoneal cavity. Bw cells are also distinct from both B-1 and B-2 cells from a functional point of view both by proliferative responses, cytokine secretion and Ab synthesis. Moreover, transfer experiments show that bone marrow and fetal liver cells from wild mice can give rise to Bw cells in alymphoid mice. The conservation of this B cell population, but not of the CD5+ B-1a, during evolution of the genus Mus, its readiness to respond to TLR ligands and to produce high concentration of autoantibodies suggest that Bw cells play a key role in innate immunity.

Identification of Initiator B Cells, a Novel Subset of Activation-Induced Deaminase-Dependent B-1-Like Cells That Mediate Initiation of Contact Sensitivity

“…Although it is clear that CD5 expression can be used to enrich for PerC cells with initiator activity, it may not define the population because we previously found that transfer of either CD5 ϩ or CD5 Ϫ CD11b ϩ PerC cells could transfer initiation (1,3). CD5 expression may be induced or further up-regulated on initiator B cells activated by sensitization, as all B cells are capable of expressing CD5 when activated (10,11). Thy-1 is also a marker for B cell activation (34) and may also be induced on initiator B cells after they reach the spleen.…”

“…Those studies that use high expression of IgM to define B-1 cells would similarly not discriminate B-1 cells from initiator B cells (16)). All of this is further complicated by the fact that B-1 cells, as defined by strict modern phenotypic criteria, are found only in laboratory strains of mice derived from M. musculus domesticus, but not other strains of mice (10), suggesting that there is heterogeneity in the phenotype and perhaps function and development of the minor B cell subsets across species. Regardless, it is clear that these minor populations have very important roles in the control of immune responses in health and disease and further investigation into defining B cell subsets and their function will become increasingly important as we seek to manipulate immune diseases through these pathways.…”

“…B cells are divided into several populations including B-2, B-1a and b, and marginal zone B cells, and recent evidence strongly suggests the existence of additional populations (10). Our previous studies identified the B cells responsible for CS initiation as a population of B-1 cells, based on their expression of CD11b in the PerC and CD5 in the spleen (1,2,4,7).…”

A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice

“…They lack CD43, CD5, and Mac-1 expression ( Figure 1C), so they are neither B1 B cells nor Bw cells recently described in wild mice (CD5 Ϫ Mac-1 ϩ B220 hi IgM hi IgD hi CD43 Ϫ CD9 Ϫ ). 23 Furthermore, they express IgM levels similar to FO B cells but lower levels of IgD. They are not activated, because MHC-II and CD86 levels are comparable with FO B cells ( Figure 1C).…”

Role of retinoic acid in the imprinting of gut-homing IgA-secreting cells

“…In addition, it has been described that conventional B1 B cells are not be found in most mammals (including several mouse strains). Instead, another B cell subset (Bw B cells) has been described in most mouse strains 33. These cells are mostly found in the peritoneal cavity and the spleen and they may play an important role in the production of natural autoantibodies.…”