Neisseria gonorrhoeae kills carcinoembryonic antigen-related cellular adhesion molecule 1 (CD66a)-expressing human B cells and inhibits antibody production.
Neisseria gonorrhoeae cells (gonococci [GC]), the etiological agents for gonorrhea, can cause repeated infections. During and after gonococcal infection, local and systemic antigonococcal antibody levels are low. These clinical data indicate the possibility that GC may suppress immune responses during infection. Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1 or CD66a), a receptor for GC opacity (Opa) proteins, was shown to mediate inhibitory signals. In the present study, human B cells were activated by interleukin-2 to express CEACAM1 and then stimulated to secrete antibodies and simultaneously coincubated with Opa- and OpaI GC of strain MS11. Our results show that this OpaI GC has the ability to inhibit antibody production. The interaction of GC and CEACAM1 with human peripheral B cells also results in induction of cell death. The same findings were observed in DT40 B cells. This CEACAM1-promoted cell death pathway does not involve the inhibitory signals or the tyrosine phosphatases SHP-1 and SHP-2 but depends on Bruton's tyrosine kinase in DT40 cells. Our results suggest that Neisseria gonorrhoeae possesses the ability to suppress antibody production by killing CEACAM1-expressing B cells.
Pantelic
Milica
M
Department of Microbiology and Immunology, Division of Infectious Diseases, Walther Oncology Center, Indiana University School of Medicine, MS415E, 635 Barnhill Dr., Indianapolis, Indiana 46202-5120, USA.
Kim
Young-June
YJ
Bolland
Silvia
S
Chen
Ines
I
Shively
John
J
Chen
Tie
T
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology*; D000943:Antigens, Differentiation / Q000032:analysis / Q000502:physiology*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D015815:Cell Adhesion Molecules; D016923:Cell Death; D002460:Cell Line; D002645:Chickens; D004792:Enzyme Precursors / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D009344:Neisseria gonorrhoeae / Q000472:pathogenicity*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D000072377:Syk Kinase
D015703:Antigens, CD; D000943:Antigens, Differentiation; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D004792:Enzyme Precursors; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; C090348:Opa protein, Neisseria; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000606896:SYK protein, human; D000072377:Syk Kinase