Newly Identified Immune Receptor Activates B Cells in Autoimmunity

A newly identified immune protein influences each person's response to vaccines and risk for autoimmune diseases like systemic lupus erythematosus (SLE) and multiple sclerosis.

A genetic variant present in approximately 15% of the world population can express an additional immune system receptor on their B cells, the cells that make antibodies. This additional receptor, called an Fc receptor, binds the antibodies made by B cells and plays a key role in regulating their production.

Scientists at the University of Alabama (Birmingham, AL, USA) determined the expression and functional properties of the Fc fragment of immunoglobulin gamma (IgG), Low Affinity IIc, Receptor (CD32) FcγRIIc in human B cells, by performing studies with B cells isolated from peripheral blood from genotyped healthy participants and from cell lines. DNA from 366 individuals enrolled into the four-dose vaccination groups and from 525 individuals enrolled into the three-dose vaccination group was used. Individuals were of European American or African American ancestry as determined by self-report and principal components analysis. There were 1,194 patients with SLE as participants and 1,656 controls.

Several different techniques were used including reverse transcription polymerase chain reaction (RT-PCR), immunocytochemistry, in vitro stimulation, enzyme-linked immunosorbent assay, immunoprecipitation, and immunoblots. Total ribonucleic acid (RNA) was prepared from cells using TRIzol Reagents (Invitrogen Life Technologies; Grand Island, NY, USA). The RT-PCR for Fc fragment of IgG, Low Affinity IIa, Receptor (FCGR2A), FCGR2B, and FCGR2C genes was performed using the Invitrogen Life Technologies’ SuperScript III First-Strand kit followed by PCR with gene-specific primers.

The authors found that this variant turns a gene that is normally silent into one that is expressed on B cells. This variant is shown to be a risk factor for the development of the autoimmune disease SLE. Patients with SLE have B cells that make antibodies that fight the body's own cells and tissues. Expression of this receptor likely contributes to this inappropriate antibody production by altering the balance of B cell activity. By analyzing antibody responses to vaccine, the team found higher antibody levels after vaccination in individuals with this genetic variant. This means individuals with the variant have enhanced early vaccine responses, and they show quicker antibody responses. Consequently, people with this variant mutation may have an advantage in fighting off infections.

Robert Kimberly, MD, the corresponding author of the study, said, “This new finding could play a significant role in the way companies design treatments for autoimmune diseases, in a more targeted approach. Now efforts can be made to target the individuals who will benefit from the treatments, based on the gene mutation.” The study was published on December 18, 2013, in the journal Science Translational Medicine.

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