Memory CD73(+)IgM(+)B cells protect againstPlasmodium yoelii infection and express Granzyme B
PLOS ONE
Authors: Parra, Marcela; Weitner, Megan; Yang, Amy; Akue, Adovi; Liu, Xia; Schmidt, Thomas; Allman, Windy R.; Akkoyunlu, Mustafa; Derrick, Steven C.
Abstract
To better understand anti-malaria protective immune responses, we examined the cellular mechanisms that govern protective immunity in a murinePlasmodium yoelii17X NL (PyNL) re-infection model. Initially, we confirmed that immune B cells generated during a primary PyNL infection were largely responsible for protection from a second PyNL infection. Using the previously identified memory B cell markers CD80, PD-L2, and CD73, we found an increase in the frequency of CD80(-)PD-L2(-)CD73(+)B cells up to 55 days after a primary PyNL infection and at 4-6 days following a second PyNL infection. Moreover, injection of enriched immune CD19(+)CD73(+)B cells into nonimmune mice were significantly more protective against a PyNL infection than CD73(-)B cells. Interestingly, a substantial fraction of these CD73(+)B cells also expressed IgM and granzyme B, a biomolecule that has been increasingly associated with protective responses against malaria.
Concepts in immuno-oncology: tackling B cell malignancies with CD19-directed bispecific T cell engager therapies
ANNALS OF HEMATOLOGY
Authors: Viardot, Andreas; Locatelli, Franco; Stieglmaier, Julia; Zaman, Faraz; Jabbour, Elias
Abstract
The B cell surface antigen CD19 is a target for treating B cell malignancies, such as B cell precursor acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma. The BiTE (R) immuno-oncology platform includes blinatumomab, which is approved for relapsed/refractory B cell precursor acute lymphoblastic leukemia and B cell precursor acute lymphoblastic leukemia with minimal residual disease. Blinatumomab is also being evaluated in combination with other agents (tyrosine kinase inhibitors, checkpoint inhibitors, and chemotherapy) in various treatment settings, including frontline protocols. An extended half-life BiTE molecule is also under investigation. Patients receiving blinatumomab may experience cytokine release syndrome and neurotoxicity; however, these events may be less frequent and severe than in patients receiving other CD19-targeted immunotherapies, such as chimeric antigen receptor T cell therapy. We review BiTE technology for treating malignancies that express CD19, analyzing the benefits and limitations of this bispecific T cell engager platform from clinical experience with blinatumomab.