Abstract
Peritoneal B-1a cells manifest unusual signaling characteristics that distinguish them from splenic B-2 cells. These include the failure of BCR engagement to trigger NF-κB activation and DNA replication. Despite extensive study, a clear explanation for these characteristics has not emerged. Here we aim to develop a unified paradigm based on previous reports and recent results, which proposes a central role for phosphatase activity. We hypothesize B-1a cells are unable to induce NF-κB or proliferate after BCR cross-linking due to increased phosphatase abundance or activity. This phosphatase abundance and/or activity may be the result of unique B-1a cell characteristics such as increased levels of HSP70 and/or constitutive secretion of IL-10. We speculate phosphatase activity cannot be overcome by BCR ligation alone due to insufficient Vav protein expression, which does not allow for proper production of reactive oxygen species, which inhibit phosphatases. Furthermore, constitutively active Lyn also plays a negative regulatory role in B-1a. We expect that a new focus on phosphatase activity and its suppression will be revealing for BCR signal transduction in B-1 cells.
Highlights
Peritoneal B-1a cells manifest unusual signaling characteristics that distinguish them from splenic B-2 cells
We hypothesize B-1a cells are unable to induce NF-κB or proliferate after BCR cross-linking due to increased phosphatase abundance or activity.This phosphatase abundance and/or activity may be the result of unique B-1a cell characteristics such as increased levels of HSP70 and/or constitutive secretion of IL-10
We speculate phosphatase activity cannot be overcome by BCR ligation alone due to insufficient Vav protein expression, which does not allow for proper production of reactive oxygen species, which inhibit phosphatases
Summary
Peritoneal B-1a cells manifest unusual signaling characteristics that distinguish them from splenic B-2 cells. The B-1a cell population originates during fetal life and persists throughout adult life by their ability to self-renew, meaning new B-1a cells are generated by mitosis of mature surface Ig-expressing B-1a cells This process is regulated in a feedback fashion [5, 6]. Housekeeping natural antibodies assist in elimination of toxic molecules such as oxidized low density lipoprotein (oxLDL), in particular by antibodies bearing the T15 idiotype, which helps control the inflammatory process leading to atherosclerotic plaques [20] These diverse functions may be facilitated by the characteristic polyreactivity of B-1a cell Ig. Beyond spontaneous secretion of natural IgM antibody, B1a cells express other distinct functions not shared by resting conventional B-2 cells. PMA responsiveness in B-1a cells is associated with rapid induction of cyclin D2 and activation of RB-phosphorylating cyclin D3-cdk complexes, neither of which www.frontiersin.org
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