An unexpected role for a white blood cell called the Natural Killer (NK) cell – a critical cell for ridding the body of infection and cancer, has been discovered by researchers at New Zealand’s University of Otago .
The NK cell is a “vigilante” killer – a white blood cell that destroys invaders and cancer cells through a process of “identity card” checking. The researchers’ new work shows that violent vigilante NK cells act as helper cells to start up the immune response.
Otago Associate Professor Alex McLellan says NK cells patrol the body and destroy abnormal cells, especially infected or cancer cells. NK cells closely examine the surface of all cells and look for molecules that are present on healthy cells.
“Certain molecules act like identity cards, and NK cell are vigilantes, ready to respond if they don’t see an ID card on cells. During infections or with cancer, the absence of these molecules triggers the NK cells to destroy the cells,” says Associate Professor McLellan.
Dr Sarah Saunderson and Associate Professor McLellan, who both work in Otago’s Department of Microbiology and Immunology, have identified a new way that NK cells act during infections or cancer.
“A few years’ ago we showed that NK cells were required for the vaccination response against cancer.” The group has now recognised that NK cells enhance the ability of the immune system to recognise fragments of tumour cells released into the blood,” says Associate Professor McLellan.
These fragments induce potent immune responses against cancer, he says.
Endogenous cell expansion within the spleen in response to B cell–derived exosomes
Splenic primary B cells were activated via CD40 and the IL-4 receptor for 3 d, then cultured with OVA protein (OVA pro) for a further 2 d. Exosomes (BcExo-pro) were isolated from culture supernatant by differential centrifugation and sucrose cushion purification. (A) Exosomes were visualized by cryoelectron microscopy. Original magnification 320,000. Scale bar, 100 nm. Image representative of three exosome preparations. (B) Exosomes were bound to 4 mm of aldehyde-sulfate beads, stained with anti– MHC-I, –MHC-II, -Ig, -CD19, -CD45R (B220), and -CD81 mAb, and analyzed by flow cytometry. Gray shaded peak indicates BSA beads; black line indicates Exo-beads. Results are representative of three exosome preparations. (C) B cell lysate (CL) or B cell–derived exosome (Exo) samples (10 or 20 mg as stated) were probed by Western blot for the presence of calnexin, MFG-E8, and CD138 (10 mg/lane), or for 14-3-3g and Alix (20 mg/lane). Results are representative of at least two exosome preparations. (D) B6 mice were immunized i.v. with PBS or 25 mg of BcExo-pro. Five days postimmunization, spleens were analyzed by flow cytometry for absolute numbers of NK cells. Results were representative of two experiments of three to five mice per group. (E) Alternatively, mice were mock- (control Ab) or NK cell–depleted 2 d prior to BcExo-pro immunization (undepleted mice immunized with PBS) and analyzed 7 d later for absolute numbers of CD4 T cells, CD8 T cells, and B cells. Results are representative of one experiment with six mice per group. Line indicates mean. Unpaired two-tailed t test (D) or one-way ANOVA with Bonferroni postcorrection (E) was performed: *p , 0.05, **p , 0.01. ns, not
“Our new work shows that NK cells are absolutely critical for the immune activity of these cell fragments.”
These latest findings also explain how such potent immune responses arise against cell fragments.
“This work also reveals new ways that NK cells help the immune system, aside from in their rather violent vigilante role.”
The group is currently looking at ways to improve NK cell function through living vaccines and growth factors to enhance the immune response to cancer.
Source – Eurekalert