A scientific team reports the discovery of the presence of a new subtype of innate lymphoid cells in human spleen essential for the production of antibodies. This discovery (“Innate lymphoid cells integrate stromal and immunological signals to enhance antibody production by splenic marginal zone B cells”), published in Nature Immunology, clears the path for the identification of novel strategies to develop more efficient vaccines against encapsulated bacteria, considered highly virulent, according to the researchers.
The work was done by the B-cell biology research group at the Institut Hospital del Mar d'Investigacions Mediques (IMIM) in Barcelona, directed by Andrea Cerutti, Ph.D., Institucio Catalana de Recerca research professor. Among the collaborators of the group are researchers from Icahn School of Medicine at Mount Sinai in New York and Riken Research Center for Integrative Medicine in Japan.
Innate lymphoid cells represent the first line of immunological defense on our body surfaces, which are constantly exposed to bacteria, such as the intestine or skin.
“For the first time both their presence and function in human spleen [have been described]. We have discovered how these cells regulate the innate immune response of a subset of splenic B lymphocytes that are responsible to fight against encapsulated bacteria, causative agents of meningitis or pneumonia,” said Giuliana Magri, M.D., member of the research group of B Cell Biology at IMIM and first author in the paper. “This new finding improves our understanding on how the immune system protects us against infections.”
“The current available vaccines against encapsulated bacteria confer only a limited protection in immunodeficient patients, and are too expensive to be implemented in developing countries,” noted Dr. Cerutti. “At the same time, we lack information on the underlying mechanisms that regulate B lymphocytes, which has been a major hurdle in the development of novel vaccine strategies. This makes the current discovery key in the design of novel, more efficient, and well-oriented therapies.”
The research involved in vitro studies with isolated cells from human spleen samples and in vivo studies performed with different mouse models. The work explored the function of the innate lymphoid cells in homeostasis, i.e., in the absence of any illness.
“We identified RORγt+ ILCs [innate lymphoid cells] near the marginal zone (MZ), a splenic compartment that contains innate-like B cells highly responsive to circulating T cell–independent (TI) antigens. Splenic ILCs established bidirectional crosstalk with MAdCAM-1+ marginal reticular cells by providing tumor-necrosis factor and lymphotoxin, and they stimulated MZ B cells via B cell–activation factor (BAFF), the ligand of the costimulatory receptor CD40 (CD40L) and the Notch ligand Delta-like 1 (DLL1),” wrote the investigators.
“Splenic ILCs further helped MZ B cells and their plasma-cell progeny by coopting neutrophils through release of the cytokine GM-CSF. Consequently, depletion of ILCs impaired both pre- and post-immune TI antibody responses. Thus, ILCs integrate stromal and myeloid signals to orchestrate innate-like antibody production at the interface between the immune system and circulatory system.”
The scientists believe their findings open the door to study the possible implication of innate lymphoid cells in diverse pathological processes both at the mucosal and systemic level, as well as deepening our understanding of autoimmune and immunodeficient diseases.