CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production

2016 ◽  
Vol 54 (12) ◽  
pp. 1343-1404
Author(s):  
V Khairnar ◽  
V Duhan ◽  
JR Göthert ◽  
PA Lang ◽  
BB Singer ◽  
...  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Vishal Khairnar ◽  
Vikas Duhan ◽  
Sathish Kumar Maney ◽  
Nadine Honke ◽  
Namir Shaabani ◽  
...  

2020 ◽  
Vol 11 ◽  
Author(s):  
Mookmanee Tansakul ◽  
Arthid Thim-uam ◽  
Thammakorn Saethang ◽  
Jiradej Makjaroen ◽  
Benjawan Wongprom ◽  
...  

Author(s):  
Panagiotis Karagiannis ◽  
Isabel Correa ◽  
Jitesh Chauhan ◽  
Anthony Cheung ◽  
Diana Dominguez-Rodriguez ◽  
...  

Abstract Human B cells and their expressed antibodies are crucial in conferring immune protection. Identifying pathogen-specific antibodies following infection is possible due to enhanced humoral immunity against well-described molecules on the pathogen surface. However, screening for cancer-reactive antibodies remains challenging since target antigens are often not identified a priori and the frequency of circulating B cells recognising cancer cells is likely very low. We investigated whether combined ex vivo culture of human B cells with three innate stimuli, interleukin-17 (IL-17), B cell activation factor (BAFF) and the toll like receptor 9 (TLR-9) agonist DNA motif CpG ODN 2006 (CpG), each known to activate B cells through different signalling pathways, promote cell activation, proliferation and antibody production. Combined IL-17+BAFF+CpG prolonged B cell survival and increased proliferation compared with single stimuli. IL-17+BAFF+CpG triggered higher IgG secretion, likely by activating differentiated, memory and class-switched CD19 +CD20 +CD27 +IgD - B cells. Regardless of anti-FOLR antibody seropositive status, IL-17+BAFF+CpG combined with a monovalent tumour-associated antigen (folate receptor alpha (FOLR)) led to secreted antibodies recognising the antigen and the antigen-expressing IGROV1 cancer cells. In a seropositive individual, FOLR stimulation favoured class-switched memory B cell precursors (CD27 -CD38 -IgD -), class-switched memory B cells and anti-FOLR antibody production, while IL-17+BAFF+CpG combined with FOLR, promoted class-switched memory B cell precursors and antibody-secreting (CD138+IgD-) plasma cells. Furthermore, IL-17+BAFF+CpG stimulation of peripheral blood B cells from patients with melanoma revealed tumour cell-reactive antibodies in culture supernatants. These findings suggest that innate signals stimulate B cell survival and antibody production and may help identify low-frequency antigen-reactive humoral responses.


Diabetes ◽  
1979 ◽  
Vol 28 (12) ◽  
pp. 1108-1113 ◽  
Author(s):  
A. Rabinovitch ◽  
T. Russell ◽  
D. H. Mintz

2000 ◽  
Vol 192 (2) ◽  
pp. 171-182 ◽  
Author(s):  
Hitoshi Nagaoka ◽  
Yoshimasa Takahashi ◽  
Reiko Hayashi ◽  
Tohru Nakamura ◽  
Kumiko Ishii ◽  
...  

Ras is essential for the transition from early B cell precursors to the pro-B stage, and is considered to be involved in the signal cascade mediated by pre-B cell antigen receptors. To examine the role of p21ras in the late stage of B cell differentiation, we established transgenic mice (TG) expressing a dominant-inhibitory mutant of Ha-ras (Asn-17 Ha-ras) in B lineage cells at high levels after the early B cell precursor stage. Expression of p21Asn-17 Ha-ras was associated with a prominent reduction in the number of late pre-B cells, but had little effect on proliferation of early pre-B cells. Inhibition of p21ras activity markedly reduced the life span of pre-B cells, due, at least in part, to downregulation of the expression of an antiapoptotic protein, Bcl-xL. Thus, the apparent role for p21ras activity in pre-B cell survival may explain the decreased numbers of late pre-B cells in Asn-17 Ha-ras TG. Consistent with this possibility, overexpression of Bcl-2 in Asn-17 Ha-ras TG reversed the reduction in the number of late pre-B cells undergoing immunoglobulin light chain gene (IgL) rearrangement and progressing to immature B cells. These results suggest that p21ras mediates effector pathways responsible for pre-B cell survival, which is essential for progression to the late pre-B and immature B stages.


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