The role of delta-class B cell receptors in immunological tolerance and autoimmunity

• Antragsteller: Professor Dr. Hassan Jumaa
• Fachliche Zuordnung: Immunologie
• Förderung: Förderung von 2010 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 179313158

In order to avoid states of autoimmunity, developing B cells need to be carefully selected in terms of their antigen specificities. Antigen specificity is determined by recombined immunoglobulin variable regions, which initially are expressed with the μ-constant region to form an IgM B cell receptor (BCR). Later in development, IgM and IgD (with the δ-constant region) BCRs are co-expressed, with predominant expression of the latter during further development. While available data pointed to a certain role in B cell development and signalling, the reason for this transition is still unclear. Recently, the description of IgD-switched autoreactive B cells has implicated IgD-BCRs in processes of immunological tolerance. In previous experiments, we could show that IgD BCRs were capable of silencing autoreactive immunoglobulin heavy chain variable regions. Autoreactivity was even silenced when silencing by receptor editing failed. Based on our observations, we hypothesise that transition from IgM to IgD may be an important safety net of the immune system and may play an unexpected and yet undescribed role in B cell selection and in the regulation of immunological tolerance. Using knock-in and in vitro reconstitution approaches, we would like to analyse the role of Ig-δ in B cell selection and autoimmunity.

• DFG-Verfahren: Sachbeihilfen