The dura mater maintains B cell lymphopoietic capacity during chronic Trypanosoma brucei infection

The dura mater hosts a rich population of B cell progenitors, but its capacity to sustain B cell development during systemic lymphopenia remains unclear. Using a murine model of chronic Trypanosoma brucei infection, which induces peripheral B cell depletion, we demonstrate that the dura mater maintains intact B cell lymphopoiesis independently of bone marrow and spleen in both male and female mice, in a process involving various chemotactic and pro-survival factors derived from the dura mater stroma. Furthermore, dura mater-derived B cells exhibit a distinct immunoglobulin repertoire that is distinct from the splenic repertoire and is dominated by Ighv1 family members. The immunoglobulins produce locally at the CNS borders are polyreactive and able to recognise both CNS and parasite antigens. Lastly, adoptive transfer of dura mater B cells, or their cognate antibodies, into B cell-deficient mice delays parasitemia onset, whereas splenic B cells from infected hosts fail to confer similar protection. These findings identify, for the first time, the dura mater as a resilient, autonomous B cell lymphopoietic niche that shapes specialized humoral responses during chronic infection, highlighting its potential role in coordinating immune defense when conventional lymphoid organs are compromised.