A CD25− Positive Population of Activated B1 Cells Expresses LIFR and Responds to LIF

Abstract

B1 B cells defend against infectious microorganisms by spontaneous secretion of broadly reactive “natural” immunoglobulin that appears in the absence of immunization. Among many distinguishing characteristics, B1 B cells display evidence of activation that includes phosphorylated STAT3. In order to identify the origin of pSTAT3 we examined interleukin-2 receptor (IL-2R) expression on B1 cells. We found that some (about 1/5) B1a cells express the IL-2R α chain, CD25. Although lacking CD122 and unresponsive to IL-2, B1a cells marked by CD25 express increased levels of activated signaling intermediates, interruption of which results in diminished CD25. Further, CD25+ B1a cells contain most of the pSTAT3 found in the B1a population as a whole. Moreover, CD25+ B1a cells express leukemia inhibitory factor receptor (LIFR), and respond to LIF by upregulating pSTAT3. Together, these results define a new subset of B1a cells that is marked by activation-dependent CD25 expression, expresses substantial amounts of activated STAT3, and contains a functional LIFR.

A Novel Mechanism of B Cell–Mediated Immune Suppression through CD73 Expression and Adenosine Production

“…Rather, CD73 identifies a specific CD73 hi subset that differs little from CD73 − B-1 cells in many functional parameters with the notable exception of ectoezyme activity. However, CD73 expression is not the only surface antigen that distinguishes B-1 cell subpopulations, as B-1 cell phenotypic heterogeneity extends to expression of PD-L2 (45), CD80 (61), CD25 (47), PC1 (48) and CD5 (42). Interestingly, Shlomchik’s group recently reported that CD73, PD-L2 and CD80 are expressed by some memory B (Bmem) cells, suggesting that Bmem cells are phenotypically heterogeneous (50, 51), much like B-1 cells.…”

“…B-1a cells are the primary source of natural antibody which can also be contributed by marginal zone B cells whereas B-1b cells contribute long lasting memory to some kinds of bacteria or virus infections (43) (44). In addition to CD5, recent studies have revealed that B-1 cell populations can be subdivided based on the expression of PD-L2 (CD273) (45, 46), CD25 (47) and PC1 (also termed ENPP1) (48). It was originally reported that CD73 is expressed on a few mouse splenic B cells (49) and more recent data show that CD73 is expressed by memory B (Bmem) cells (50, 51).…”

Expression of plasma cell alloantigen 1 defines layered development of B-1a B-cell subsets with distinct innate-like functions

“…The Rothstein and Herzenberg laboratories identified a CD11b − B-1a subset in the peritoneum (9,56), questioning the reliability of CD11b as a pan B-1 cell marker that has been widely used for positive gating on B-1a and B-1b cells. Recently, Rothstein and coworkers identified PD-L2 + (57) and CD25 + B-1a subsets (58). By using a decoy receptor for many CC chemokines, D6, as a marker, Hansell et al described the division of B-1a cells into four subpopulations (59).…”

CD25+ B-1a Cells Express Aicda

“…The expression level of Aicda was evaluated in sort-purified peritoneal B-1a cells, peritoneal CD25 + B-1a cells (4), peritoneal CD25 − B-1a cells, splenic B2 cells, and GC B cells from unmanipulated mice. The sorting strategy for isolating these populations is shown in Figure 1A.…”

“…However, these B-1a cells lack expression of CD122 and are not responsive to IL-2 (4). In some systems, AID expression appears to impact viability.…”