Putative IgD binding proteins of Neisseria species

Abstract

Neisseria lactamica is a commensal bacterium of the upper respiratory tract. It is closely related to Neisseria meningitidis; an opportunistic pathogen that asymptomatically colonises the upper respiratory tract, but under certain circumstances, causes invasive disease. In this thesis, it is demonstrated that outer membrane vesicles extracted from Neisseria lactamica, N. cinerea, N. flavescens and N. polysaccharea induce proliferation of peripheral blood-derived B cells. Furthermore, this proliferative response is specific to B cells expressing IgDλ cell surface receptors. Pre-treatment of B cells with F(ab’)2 polyclonal goat anti-human IgD and λ light chain antibodies reduced the proliferation in response to N. lactamica, N. cinerea, N. flavescens and N. polysaccharea. It is also shown here that this phenotype is not shared among all Neisseria since the outer membrane vesicles extracted from N. elongata, N. subflava, N. mucosa, N. macacae, N. gonorrhoea and N. meningitidis are unable to induce a proliferative response in B cells.
Two genes of N. lactamica with homology to Moraxella catarrhalis IgD binding protein were identified. Both genes were experimentally knocked out, generating two single knockout strains (ΔNLY_37260 and ΔNLY_36660) and one double knockout strain (ΔNLY_36660 ΔNLY_37260). The double knockout strain does not induce proliferation of B cells expressing IgDλ, while single knockout strains are still mitogenic for IgDλ+ B cells, albeit at reduced levels, suggesting N. lactamica contains two IgD binding proteins, with redundancy between them.
Additionally, homologues of Moraxella catarrhalis IgD binding protein MID have been identified in N. cinerea, N. flavescens and N. polysaccharea and experimentally knocked out. Unlike wild-type strains, all knockout strains lacking the gene for putative IgDbp lack the ability to induce proliferation in IgDλ+ B cells. These knockout strains may be used as tools to further explore the putative IgDλ binding protein present in commensal Neisseriaspp.
In summary, this work shows that N. lactamica induces an IgDλ+ B cell proliferative response likely due to the presence of an IgDλ binding protein, a characteristic shared by N. cinerea, N. flavescens and N. polysaccharea. This response may play an important role in evasion of the adaptive immune system of the upper respiratory tract, analogous to the activation of intestinal B cells and subsequent production of sIgA.

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Identifiers

ORCID for Muhammad Ahmed: orcid.org/0000-0003-3234-2788

ORCID for Robert Read: orcid.org/0000-0002-4297-6728

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