His group, in collaboration with scientists in Mount Sinai in New York, has just discovered the presence of neutrophils in the marginal zone (MZ) of the spleen, a B cell area positioned at the interface between the circulation and the immune system. The presence of these cells is constant, even in the absence of infection.
The authors obtained lymphoid organs from people with no inflammation or infection. Unexpectedly, they detected many neutrophils in the perifollicular area of spleens that had no histological alterations – up to 10% of the total cells in the spleens were neutrophils. They also detected perifollicular neutrophils in spleens from healthy rhesus macaques and mice, suggesting these spleen neutrophils are probably common to all mammals.
They compared this newly found population of neutrophils with the circulating ones, and found they had a distinct phenotype. They also had a different function: they interacted with marginal zone B cells, and elicited immunoglobulin class switching, somatic hypermutation and antibody production by activating those B cells via BAFF and APRIL and the cytokine IL-21 – an immunoregulatory function that is new to neutrophils.
Being strategically located at the interface with the circulation, the major role of the marginal zone is to trap particulate antigen from the circulation and present them to the lymphocytes of the spleen. Marginal zone B cells are therefore geared to rapidly respond to blood-borne antigens. The authors believe that the discovered spleen neutrophils may generate an innate layer of antimicrobial immunoglobulin defense by undergoing B cell–helper reprogramming in the spleen. Actually, they found these ‘B cell–helper neutrophils’ to activate marginal zone B cells as effectively as splenic CD4+ T cells, and more effectively than splenic macrophages or dendritic cells (DCs).
Cerutti and colleagues conclude that an insufficiency of these ‘B cell–helper neutrophils’ could contribute to the pathogenesis of systemic infections in patients with neutrophil disorders. Conversely, harnessing these cells with specific adjuvants may enhance vaccine-induced immunoglobulin responses to poorly immunogenic antigens in healthy people.
Puga I, Cols M, Barra CM, He B, Cassis L, Gentile M, Comerma L, Chorny A, Shan M, Xu W, Magri G, Knowles DM, Tam W, Chiu A, Bussel JB, Serrano S, Lorente JA, Bellosillo B, Lloreta J, Juanpere N, Alameda F, Baró T, de Heredia CD, Torán N, Català A, Torrebadell M, Fortuny C, Cusí V, Carreras C, Diaz GA, Blander JM, Farber CM, Silvestri G, Cunningham-Rundles C, Calvillo M, Dufour C, Notarangelo LD, Lougaris V, Plebani A, Casanova JL, Ganal SC, Diefenbach A, Aróstegui JI, Juan M, Yagüe J, Mahlaoui N, Donadieu J, Chen K, & Cerutti A (2011). B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen. Nature immunology PMID: 22197976