SLAP Deficiency Decreases DsDNA Autoantibody Production

Overview

Journal Clin Immunol

Specialty Allergy & Immunology

Date 2014 Jan 21

PMID 24440645

Citations 2

Authors

Lisa K Peterson

Luke F Pennington

Laura A Shaw

Meredith Brown

Eric C Treacy

Samantha F Friend

Oyvind Hatlevik

Kira Rubtsova

Anatoly V Rubtsov

Leonard L Dragone

Affiliations

Soon will be listed here.

Abstract

Src-like adaptor protein (SLAP) adapts c-Cbl, an E3 ubiquitin ligase, to activated components of the BCR signaling complex regulating BCR levels and signaling in developing B cells. Based on this function, we asked whether SLAP deficiency could decrease the threshold for tolerance and eliminate development of autoreactive B cells in two models of autoantibody production. First, we sensitized mice with a dsDNA mimetope that causes an anti-dsDNA response. Despite equivalent production of anti-peptide antibodies compared to BALB/c controls, SLAP(-/-) mice did not produce anti-dsDNA. Second, we used the 56R tolerance model. SLAP(-/-) 56R mice had decreased levels of dsDNA-reactive antibodies compared to 56R mice due to skewed light chain usage. Thus, SLAP is a critical regulator of B-cell development and function and its deficiency leads to decreased autoreactive B cells that are otherwise maintained by inefficient receptor editing or failed negative selection.

Citing Articles

Phenotyping of autoreactive B cells with labeled nucleosomes in 56R transgenic mice.

Gies V, Bouis D, Martin M, Pasquali J, Martin T, Korganow A Sci Rep. 2017; 7(1):13232.

PMID: 29038433 PMC: 5643551. DOI: 10.1038/s41598-017-13422-z.

Role of SRC-like adaptor protein (SLAP) in immune and malignant cell signaling.

Kazi J, Kabir N, Ronnstrand L Cell Mol Life Sci. 2015; 72(13):2535-44.

PMID: 25772501 PMC: 11113356. DOI: 10.1007/s00018-015-1882-6.

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