Neisseria lactamica selectively induces mitogenic proliferation of the naive B cell pool via cell surface Ig.
Neisseria lactamica is a commensal bacteria that colonizes the human upper respiratory tract mucosa during early childhood. In contrast to the closely related opportunistic pathogen Neisseria meningitidis, there is an absence of adaptive cell-mediated immunity to N. lactamica during the peak age of carriage. Instead, outer membrane vesicles derived from N. lactamica mediate a B cell-dependent proliferative response in mucosal mononuclear cells that is associated with the production of polyclonal IgM. We demonstrate in this study that this is a mitogenic human B cell response that occurs independently of T cell help and any other accessory cell population. The ability to drive B cell proliferation is a highly conserved property and is present in N. lactamica strains derived from diverse clonal complexes. CFSE staining of purified human tonsillar B cells demonstrated that naive IgD(+) and CD27(-) B cells are selectively induced to proliferate by outer membrane vesicles, including the innate CD5(+) subset. Neither purified lipooligosaccharide nor PorB from N. lactamica is likely to be responsible for this activity. Prior treatment of B cells with pronase to remove cell-surface Ig or treatment with BCR-specific Abs abrogated the proliferative response to N. lactamica outer membrane vesicles, suggesting that this mitogenic response is dependent upon the BCR.
Vaughan
Andrew T
AT
Department of Cellular and Molecular Medicine, School of Medical Science, University of Bristol, Bristol, United Kingdom. andrew.vaughan@soton.ac.uk
Brackenbury
Louise S
LS
Massari
Paola
P
Davenport
Victoria
V
Gorringe
Andrew
A
Heyderman
Robert S
RS
Williams
Neil A
NA
D056704:Adaptive Immunity / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007072:Immunoglobulin D / Q000502:physiology; D007075:Immunoglobulin M / Q000502:physiology; D042806:Neisseria lactamica / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D018272:Porins / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D016192:Resting Phase, Cell Cycle / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000382:microbiology
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D018272:Porins; D011947:Receptors, Antigen, B-Cell; C057699:porin protein, Neisseria