Coronin 1 Is Essential for IgM-Mediated Ca2+ Mobilization in B Cells but Dispensable for the Generation of Immune Responses In Vivo

Abstract

Coronin 1 is a leukocyte specific regulator of Ca2+-dependent signaling and is essential for the survival of peripheral T lymphocytes, but its role in B cells is unknown. In this study, we show that coronin 1 is essential for intracellular Ca2+ mobilization and proliferation upon triggering of the BCR. However, the presence of costimulatory signals rendered coronin 1 dispensable for B cell signaling, consistent with the generation of normal immune responses against a variety of Ags in coronin 1-deficient mice. We conclude that coronin 1, while being essential for T cell function and survival, is dispensable for B cell function in vivo.

Coronin 1-Mediated Naive T Cell Survival Is Essential for the Development of Autoimmune Encephalomyelitis

“…This activation defect of naive T cells lacking coronin 1 is reflected by impaired proliferation and cytokine expression upon TCR stimulation in vitro. However, coronin 1-deficient mice are capable of mounting relatively normal Ab responses to T cell-independent, as well as T cell-dependent, Ags (24). The most striking effect of coronin 1 depletion is the apparent increased spontaneous apoptosis of naive T cells ex vivo (19,20,23).…”

“…Indeed, in the absence of coronin 1, MOG-specific T cell responses such as proliferation and cytokine expression after immunization with MOG peptide are delayed, as well as reduced, strongly suggesting a priming defect in the absence of coronin 1. In addition, several lines of evidence exclude a role for coronin 1 in Ag processing and presentation: 1) the restoration of EAE on transfer of wild-type T cells as shown in this study; 2) the absence of any defect in either macrophage, B cell, and dendritic cell function (3,24,25,38) and the absence of any gross defects in thymic selection, a process that is heavily dependent on Ag processing and presentation (19)(20)(21). Naive T cell priming, which is the initial step of an immune response, usually takes place in the draining lymph nodes where professional APCs activate naive T cells, leading to clonal expansion and differentiation into cytokine-expressing effector T cells.…”

“…Despite diminished numbers of naive T cells (20), when coronin 1-deficient mice are immunized with a variety of Ags, normal Ab responses are generated (24). To investigate the role of coronin 1 in the pathogenesis of T cell-mediated autoimmunity, we immunized coronin 1-deficient and wild-type C57BL/6 mice with MOG peptide emulsified in CFA s.c. together with pertussis toxin i.p.…”

“…Mice that lack coronin 1 have strongly reduced naive T cell numbers in the periphery, whereas thymic cellularity and selection is relatively normal (19)(20)(21)(22)(23). Interestingly, despite strongly reduced naive T cell numbers and the observed in vitro activation defect, coronin 1-deficient mice show relatively normal Ab responses to thymus-dependent and -independent Ags (24).…”

Constitutive Turnover of Phosphorylation at Thr-412 of Human p57/Coronin-1 Regulates the Interaction with Actin

“…During the phagocytic process of bacterial infection, p57/coronin-1 was shown to transiently accumulate on the surface of phagosomes and control the subsequent phagosome-lysosome fusion. Recent studies have also demonstrated that p57/coronin-1 was enriched in immunological synapses and involved in various immune regulatory functions such as signal transduction via T cell receptors (16 -18), survival of T cells (19,20), and intracellular Ca 2ϩ mobilization in T and B cells (19,21). More recently, it was reported that the p57/coronin-1 gene was responsible for human and mouse severe combined immunodeficiency (22,23).…”