Question 1

(Auto)antigen-specific plasmablasts and memory B cells

Accepted Answer

For comparison, the group studies characteristics of (auto)antigen specific plasmablast and memory B cells upon vaccination versus active autoimmune disease. Such studies address potential molecular differences between autoreactive and protective B and plasma cells which would candidate as selective target in treatment autoimmunity. Moreover, such differences can serve as biomarkers for disease activity, prognosis and/or therapeutic response.

Question 2

Molecular and functional properties of plasma cell subsets

Accepted Answer

After the original identification of unique CD19- plasma cells implying that human bone marrow plasma cells are several heterogeneous subsets, current studies address this heterogeneity by their detailed molecular and functional characteristics. In this context and within a collaborative project with Prof. Klaus Rajewsky’s group at the MDC, we apply state of the art CRISPR/Cas9 technology to identify molecular differences between normal plasma cells and autoimmune plasma cells from SLE patients that can provide the basis for innovative molecular therapies.

Question 3

Hyporesponsive or anergic post-activated (APA) B cells

Accepted Answer

In contrast to the conventional view that B lineage cells in autoimmunity are hyperresponsiveness, we originally found hyporesponsive or anergic post-activated (APA) B lineage cells in SLE, RA and Sjögren’s  based on their reduced cytokine production, TLR and especially BCR responses. Most notable and with the most striking differences, BCR activation resulted in substantially reduced protein tyrosine kinase phosphorylation of downstream molecules (Syk, BTK and PLCg-2) together with increased expression of certain surface molecules such as CD22 connected to SHP-1, a receptor related phosphatase. Overall, APA B cells carry characteristically increased protein tyrosine phosphatase which is controlled by CD40 dependent transcription. Activation of CD40 results in reduced phosphatase activity and overcomes APA B cell abnormalities including normalization of BCR responses.

Question 4

Mechanism of innovative B-cell therapeutics

Accepted Answer

Various studies on the mechanism of innovative B cell therapeutics are underway in collaboration with the Charite Research Organization and our lab which provide insights into the underlying disease and disease mechanisms and therapeutic consequences on certain lymphocytes in relation to clinical responses. Here innovative therapeutics targeting B lineage cells beyond anti-CD20 targeting hold promise for more selective and effective treatments for systemic inflammatory diseases.

B Cell Memory

Immunomodulatory approaches targeting autoreactive B lineage cells while leaving protective B memory intact

Prof. Dr. med. Thomas Dörner

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