Complexin 2 regulates secretion of immunoglobulin in antibody-secreting cells.

Ken Sawada,Emi Tsuru,Masayuki Tsuda,Kohei Oryu,Makoto Nishihara

doi:10.1002/iid3.276

Abstract

IntroductionComplexins (CPLXs), initially identified in neuronal presynaptic terminals, are cytoplasmic proteins that interact with the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors (SNARE) complex to regulate the fusion of vesicles to the plasma membrane. Although much is known about CPLX function in neuronal synaptic vesicle exocytosis, their distribution and role in immune cells are still unclear. In this study, we investigated CPLX2 knockout (KO) mice to reveal the role of CPLXs in exocytosis of lymphocytes.MethodsWe examined the expression of CPLXs and SNAREs in lymphocytes. To study the effect of CPLXs on the immune system in vivo, we analyzed the immune phenotype of CPLX2 KO mice. Furthermore, antibodies secretion from the peritoneal cavity, spleen, and bone marrow cells of wild‐type (WT) and CPLX2 KO mice were determined.ResultsCPLX2 was detected in B cells but not in T cells, while other CPLXs and SNAREs were expressed at a similar level in both B and T cells. To clarify the function of CPLX2 in B lymphocytes, serum concentrations of immunoglobulin G (IgG), IgA, IgM, and IgE were measured in WT and CPLX2 KO mice using enzyme‐linked immunosorbent assay. The level of IgM, which mainly consists of natural antibodies, was higher in KO mice than that in WT mice, while the levels of other antibodies were similar in both types of mice. Additionally, we found that spontaneous secretion of IgM and IgG1 was enhanced from the splenic antibody‐secreting cells (ASCs) of CPLX2 KO mice.ConclusionOur data suggest that CPLX2 inhibits spontaneous secretion of IgM and IgG1 from splenic ASCs. This study provides new insight into the mechanism of antibody secretion of ASCs.

Highlights

Complexins (CPLXs), initially identified in neuronal presynaptic terminals, are cytoplasmic proteins that interact with the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors (SNARE) complex to regulate the fusion of vesicles to the plasma membrane
Similar to its function in the neuronal synapse, we hypothesize that CPLXs in lymphocytes may associate with the membrane fusion machinery
Neurotransmitters are secreted by exocytosis of synaptic vesicles from the plasma membrane induced by the assembly of SNARE complex.[2]

Summary

| INTRODUCTION

Soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors (SNAREs) play a central role in regulating membrane fusion during neurotransmitter release.[1,2] Outside the neural tissues, SNARE proteins function in other membrane fusion processes, such as hormone secretion,[3] the acrosome reaction,[4] and degranulation.[5] SevSeveral studies have shown that peripheral blood cells, such as mast cells, plasma cells, neutrophils, and lymphocytes share the secretory machinery that includes the combination of subtypes of SNAP (Qbc‐SNARE), VAMP (R‐SNARE), and Syntaxin (Qa‐SNARE).[5,6,7,8,9]. We tested whether CPLX2 affects the secretion of immunoglobulins using CPLX2 KO mice

| MATERIALS AND METHODS

| RESULTS

Findings

| DISCUSSION