Biology subjects

Toellner, K.-M.

Publications and source records attributed to Toellner, K.-M..

3 recordsLinked to original sources

bioRxiv2021

Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism

Mutualistic interactions with the commensal microbiota are enforced through a range of immune responses that confer metabolic benefits for the host and ensure tissue health and homeostasis. Immunoglobulin (Ig)A responses directly determine the composition of commensal species that colonize the intestinal tract but require significant metabolic resources to fuel antibody production by tissue-resident plasma cells. Here we demonstrate IgA responses are subject to diurnal regulation by dietary-derived metabolic cues and a cell-intrinsic circadian clock. Rhythmicity in IgA secretion conferred oscillatory patterns on the commensal microbial community and its associated metabolic activity, resulting in changes to metabolite availability over the course of the circadian day. Our findings suggest circadian networks comprising intestinal IgA, the diet and the microbiota align to ensure metabolic health. One-Sentence SummaryWe demonstrate diurnal rhythms in intestinal IgA act to cross-regulate oscillations in the abundance of commensal microbes to foster mutualism.

immunology↗

bioRxiv2020

Memory-like B cells emerging from germinal centres recycle through the subcapsular sinus

Infection or vaccination leads to the development of germinal centers (GCs) where B cells evolve high affinity antigen receptors, eventually producing antibody-forming plasma cells or memory B cells. We followed the migratory pathways of B cells emerging from germinal centers (BEM) and found that many migrated into the lymph node subcapsular sinus (SCS) guided by sphingosine-1-phosphate (S1P). From there, B cells may exit the lymph node to enter distant tissues. Some BEM cells interacted with and took up antigen from SCS macrophages, followed by CCL21-guided return towards the GC. Disruption of local CCL21 gradients inhibited the recycling of BEM cells and resulted in less efficient adaption to antigenic variation. Our findings suggest that the recycling of BEM cells, that transport antigen and that contain the genetic code for B cell receptor variants, may support affinity maturation to antigenic drift.

immunology↗

bioRxiv2020

Enhanced BCR signalling inflicts early plasmablast and germinal centre B cell death

It is still not clear how B-cell receptor (BCR) signalling intensity affects plasma cell and germinal centre (GC) B cell differentiation. We generated C{gamma}1Cre/+Ptpn6fl/fl mice where SHP-1, a negative regulator of BCR signalling, is deleted rapidly after B cell activation. Although immunisation with T-dependent antigens increased BCR signalling, it led to plasma cells reduction and increased apoptosis. Dependent on the antigen, the early GC B cell response was equally reduced and apoptosis increased. At the same time, a higher proportion of GC B cells expressed cMYC, indicating increased GC B cell - Tfh cell interactions. While GC B cell numbers returned to normal at later stages, affinity maturation was suppressed in the long term. This confirms that BCR signalling not only directs affinity dependent B cell selection but also, without adequate Tfh cell help, can inflict cell death, which may be important for the maintenance of B cell tolerance.

immunology↗