2024-T-B Collaboration in Autoimmunity, Infection, and Transplantation
T-B collaboration initiates a complicated network of
sequential interactions, both direct and indirect, that
positively reinforce alloimmune antibody responses.
Disruption or modulation of this collaboration may aid
efforts to treat or prevent AMR. Selective manipulation of
isotype switching could improve outcomes, but the mechanisms
driving isotype rearrangements are poorly understood
and given their roles in other aspects of immune
responses, efforts targeting the relevant cytokines may lack
specificity. The ability to prevent allo-specific antibody
production without disrupting normal humoral response
would revolutionize organ transplantation. However, a
more sophisticated understanding of humoral responses
to alloantigen is needed before this goal can be achieved.
The relative contribution of GC versus extrafollicular antibody
production to AMR is ill-defined and may be context
dependent. Furthermore, antigen-specific interventions
are required to prevent alloantibody production without
compromising beneficial T-B collaboration or to augment
desired T-B collaboration without driving rejection. B-cell
allo-epitopes are well described, but little is known about
the T-cell epitope landscape. What types of mismatches
generate T-cell epitopes? Which ones are responsible for
AMR? What types of T-B collaboration do they lead to?
T-cell epitopes are difficult to identify, but linked recognition
may offer a roadmap forward.