Naslov
NKG2D Promotes B1a Cell Development and Protection against Bacterial Infection

Autori
Lenartić, Maja ; Jelenčić, Vedrana ; Zafirova, Biljana ; Ožanič, Mateja ; Marečić, Valentina ; Jurković, Slaven ; Sexl, Veronika ; Šantić, Marina ; Wensveen, Felix ; Polić, Bojan ;

Izvornik
Journal of immunology (0022-1767) 198 (2017), 4; 1531-1542

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
NKG2D, B1a cells, B cell development, bacterial infections
(NKG2D, B1a cells, B cell development, bacterial infection)

Sažetak
NKG2D is a potent activating receptor that is expressed on cytotoxic immune cells such as CD8 T and NK cells, where it promotes cytotoxicity after binding stress ligands on infected or transformed cells. On NK cell precursors NKG2D modulates proliferation and maturation. Previously, we observed that NKG2D deficiency affects peripheral B cell numbers. In this study, we show that NKG2D regulates B1a cell development and function. We find that mice deficient for NKG2D have a strong reduction of B1a cell numbers. As a result, NKG2D-deficient mice produce significantly less Ag-specific IgM Abs upon immunization with T cell–independent Ags, and they are more susceptible to Gram-negative sepsis. Klrk1−/− B1a cells are also functionally impaired and they fail to provide protection against Francisella novicida upon adoptive transfer. Using mixed bone marrow chimeric mice, we show that the impact of NKG2D deficiency on B1a cell development is cell intrinsic. No changes in homeostatic turnover and homing of B cells were detectable, limiting the effects of NKG2D to modulation of the hematopoietic development of B1a cells. Using conditional ablation, we demonstrate that the effect of NKG2D on B1a cell development occurs at a developmental stage that precedes the common lymphoid progenitor. Our findings reveal an unexpected new role for NKG2D in the regulation of B1a cell development. The protective effects of this activating receptor therefore reach beyond that of cytotoxic cells, stimulating the immune system to fight bacterial infections by promoting development of innate-like B cells.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA