Deficient for endoplasmic reticulum calcium sensors Stim1 and Stim2 affects aberrant antibody affinity maturation in B cells

Oncotarget. 2016 Sep 20;7(38):60885-60895. doi: 10.18632/oncotarget.11659.

Abstract

Antigen specific B cells undergo a process termed affinity maturation in the germinal centers of secondary lymphoid organs where B cells with high affinity receptors are selected to mature into antibody-producing cells or to the memory B cell pool. It is known that B cell antigen receptor (BCR) signaling plays pivotal role in this selection process. Calcium influx is an essential component of BCR signaling. The current report is to determine the effect of calcium influx on antibody affinity maturation. In our studies, mice deficient for both endoplasmic reticulum calciumsensor Stim1 and Stim2 was immunized with T-cell dependent and independent antigens. Antibody affinity was measured by ELISA. We demonstrated that Stim1 &Stim2 deficient B cells exhibit accelerated pace of affinity maturation compared to wild type controls while the overall antibody production was not dramatically impaired to T-independent antigen immunization. In conclusion, calcium influx plays an important role in antibody affinity maturation in humoral immune responses. The knowledge can be used in manipulate humoral immune response for the design of effective vaccines.

Keywords: B cells; Immune response; Immunity; Immunology and Microbiology Section; Stim1; Stim2; antibody affinity; calcium influx.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Antibody Affinity
  • Antibody-Producing Cells / immunology
  • B-Lymphocytes / immunology*
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Calcium Signaling / physiology
  • Cell Proliferation
  • Crosses, Genetic
  • DNA Mutational Analysis
  • Endoplasmic Reticulum / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Immunity, Humoral
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Signal Transduction
  • Stromal Interaction Molecule 1 / metabolism*
  • Stromal Interaction Molecule 2 / metabolism*
  • T-Lymphocytes / immunology

Substances

  • Calcium Channels
  • Membrane Glycoproteins
  • Membrane Proteins
  • Stim1 protein, mouse
  • Stim2 protein, mouse
  • Stromal Interaction Molecule 1
  • Stromal Interaction Molecule 2
  • Calcium