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.

Highlights

  • In mice, B1 cells represent a unique subset of B lymphocytes originally distinguished from the more abundant conventional splenic B cells by expression of the pan-T cell marker, CD5

  • In order to elucidate the origin of pSTAT3 in B1a cells, and in view of our finding that B1 cells show evidence of continual signaling, we considered the possibility that B1 cells might express CD25/interleukin-2 receptor (IL-2R) and that IL-2R signaling might account for B1 cell activated STAT3

  • CD25+ B1a CELLS DISPLAY ELEVATED LEVELS OF PHOSPHORYLATED TYROSINE705 STAT3 Because IL-2 is capable of activating STAT3, CD25 expression by some B1a cells raises the possibility that the CD25+ B1a subset harbors all of the constitutively phosphorylated STAT3 attributed to B1 cells as a whole (Karras et al, 1997)

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Summary

Introduction

B1 cells represent a unique subset of B lymphocytes originally distinguished from the more abundant conventional splenic B cells by expression of the pan-T cell marker, CD5. B1 cells are the predominant lymphocyte population in the peritoneal and pleural cavities, are present in small numbers in the spleen, and are absent in the peripheral blood and lymph nodes (Hayakawa et al, 1983). Two B1 cell populations exist, B1a cells that express CD5, and B1b cells that lack CD5 but are otherwise phenotypically similar to B1a cells in some ways functionally distinct (Kantor et al, 1992; Alugupalli et al, 2004). Much of what is known about B1 cells concerns CD5+ B1a cells

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