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

Abstract

B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis. The absence of this signalling cascade in naive Ceacam1−/− mice limits the survival of B cells. During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1−/− mice can barely induce neutralizing antibody responses and die early after infection. We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses.

CD169+ macrophages regulate PD-L1 expression via type I interferon and thereby prevent severe immunopathology after LCMV infection

“…12, 13, 22 In this study using LCMV, we did not find reduced priming of adaptive immune cells; however, we did find reduced induction of IFN-I. There may be two reasons for these diverse functions of CD169 + macrophages in VSV infection and LCMV infection.…”

Soluble CEACAM1 and CEACAM6 are differently expressed in blood serum of pregnant women during normal pregnancy

“…As mentioned above, some members of the CEA family such as the membrane anchored CEACAM1 have immune‐modulatory functions, especially after ligand binding leading to co‐stimulation of the T‐ and B‐cell activity . Lower amounts of CEACAM1 in the serum of pregnant women also mean lower amounts of ligand for the membrane‐bound CEACAM1 as receptor and thus potentially less co‐stimulatory capacity.…”

“…According to the literature, CEACAM1 can act both as a co‐inhibitory and as a co‐stimulatory receptor molecule . In the case of the TLR‐2 (toll‐like receptor‐2), CEACAM1 inhibits the immune response if interacting with soluble CEACAM8 as ligand .…”

“…It is present in epithelial and angiogenically activated endothelial cells, as well as in various leukocyte subtypes. CEACAM1 interacts in a homotypic and heterotypic way with other CEACAMs, including CEACAM6 (CD66c) . CEACAM1 and CEACAM6 were detected in the uterine cervix and may serve as biomarkers in several pathological conditions .…”

Anti-carcinoembryonic antigen-related cell adhesion molecule antibody for fluorescence visualization of primary colon cancer and metastases in patient-derived orthotopic xenograft mouse models

“…CEACAM1, CEACAM5 and CEACAM6 are co-expressed in epithelial cells of the gastro-intestinal tract and can also be overexpressed in endometrial, lung, ovarian, cervical, breast and colon cancers [5]. CEACAMs participate in multiple physiological and pathophysiological processes, including cell-cell adhesion, epithelial differentiation, apoptosis, neo-vascularization and pro-inflammatory regulation of B-and T-cell proliferation [4,6,7]. Alterations in the expression of CEACAM are often linked to epithelial disorders and malignancies.…”