Characterization of the IgD Binding Site of Encapsulated <i>Haemophilus influenzae</i> Serotype b

Samuelsson, Martin; Hallström, Teresia; Forsgren, Arne; Riesbeck, Kristian

doi:10.4049/jimmunol.178.10.6316

Cited by 11 publications

(8 citation statements)

References 30 publications

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“…In fact, nonimmune binding of Igs by gram-positive bacteria is relatively common but rare among gram-negative bacteria (51,75). Interestingly, H. influenzae also displays a strong affinity for soluble human IgD (125), although the protein involved in IgD binding has as yet been identified only in M. catarrhalis. MID is also a B-lymphocyte mitogenic stimulant that initiates Ig production (49), and a comparison of MIDs of five strains revealed that the overall sequence identity ranged between 65.3% and 85.0%, with some regions showing an identity up to 97% (98).…”

Section: Adhesion and Major Ompsmentioning

confidence: 99%

Molecular Aspects ofMoraxella catarrhalisPathogenesis

Vries

Bootsma

Hays

et al. 2009

Microbiol Mol Biol Rev

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SUMMARY In recent years, Moraxella catarrhalis has established its position as an important human mucosal pathogen, no longer being regarded as just a commensal bacterium. Further, current research in the field has led to a better understanding of the molecular mechanisms involved in M. catarrhalis pathogenesis, including mechanisms associated with cellular adherence, target cell invasion, modulation of the host's immune response, and metabolism. Additionally, in order to be successful in the host, M. catarrhalis has to be able to interact and compete with the commensal flora and overcome stressful environmental conditions, such as nutrient limitation. In this review, we provide a timely overview of the current understanding of the molecular mechanisms associated with M. catarrhalis virulence and pathogenesis.

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Section: Adhesion and Major Ompsmentioning

confidence: 99%

Molecular Aspects ofMoraxella catarrhalisPathogenesis

Vries

Bootsma

Hays

et al. 2009

Microbiol Mol Biol Rev

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“…However, the bacteria can also be invasive in tonsillar tissue. By binding to surface IgD at the CH1 region, it is postulated to function as a superantigen . In vitro experiments have shown that H. influenzae , and also OMV‐mediated sIgD cross‐linking, result in strong proliferation of IgD+ lymphocytes, secretion of poly‐reactive IgM and IgD, production of IL6, and sensitization to BAFF .…”

Section: Discussionmentioning

confidence: 99%

Paediatric nodal marginal zone B‐cell lymphadenopathy of the neck: a Haemophilus influenzae‐driven immune disorder?

Kluin

Langerak

Beverdam-Vincent

et al. 2015

The Journal of Pathology

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Many hyperplasias and lymphomas of marginal zone B-cells are associated with infection. We identified six children and one adolescent with cervical lymphadenopathy showing prominent polyclonal nodal marginal zone hyperplasia (pNMZH) and four adolescents with monoclonal paediatric nodal marginal zone lymphoma (pNMZL). The clonality status was assessed using BIOMED-2-IG PCR analysis. Haemophilus influenzae was identified in all six cases of pNMZH that could be tested by direct culture (N = 3) or a very sensitive PCR for the H. influenzae gyrase gene in frozen materials (N = 5). H. influenzae was not detected in three pNMZLs and 28 non-specific reactive cervical lymph nodes of age-matched controls, except for a single control node that was obtained during oropharyngeal surgery for a cleft palate showing very low copy numbers of H. influenzae. pNMZH patients were younger than pNMZL patients (median age 12 versus 21 years). pNMZH showed a prominent nodular appearance with variable fibrosis without acute inflammation. Within the nodules, the expanded germinal centres and variably sized marginal zones were colonized by activated B-cells with weak expression of IgD and lack of CD10 and/or BCL6 expression. Some areas showed skewed light chain expression in plasma cells (4/5 cases lambda). In four cases tested, this was confirmed by flow cytometry for surface Ig (3/4 cases lambda). In contrast, pNMZL showed more extensive expansion of marginal zones by centrocytoid cells and often expression of BCL2 protein. Several H. influenzae strains are known to interact with the constant part of IgD on human B-cells, leading to their polyclonal proliferation and activation. We speculate that in vivo stimulation of IgD+ marginal zone B-cells by this bacterium may be implicated in this particular lymphadenopathy that should be distinguished from monoclonal pNMZL.

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“…Hypothetically, the nonimmuneactivated B cells that change from IgD ϩ /IgM ϩ to IgD -/IgM ϩ Representative results from one out of four donors are shown, and corresponding geometric mean fluorescence, SD, and P values are presented in Table 3. will later be negatively selected during affinity maturation. B cells that keep the IgD receptor will be favored in the process, and this could explain the high number of IgD ϩ plasma cells in the nasopharynx and in the middle ear cavity, areas that are frequently colonized by two pathogens (M. catarrhalis and H. influenzae) capable of binding IgD [14,[42][43][44].…”

Section: Discussionmentioning

confidence: 99%

Moraxella catarrhalis-dependent tonsillar B cell activation does not lead to apoptosis but to vigorous proliferation resulting in nonspecific IgM production

Jendholm

Samuelsson

Cardell

et al. 2008

Journal of Leukocyte Biology

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The respiratory pathogen Moraxella catarrhalis has a high affinity for human IgD and is mitogenic for peripheral blood B lymphocytes. Moraxella IgD-binding protein, which is a multifunctional outer membrane protein with adhesive properties, is responsible for the interaction. Previous experiments with the Ig-binding B cell superantigens protein A and protein L from Staphylococcus aureus and Peptostreptococcus magnus, respectively, have suggested that nonimmune BCR cross-linking induces B cell apoptosis through the intrinsic pathway. The goal of this study was to characterize early and late B cell events in the presence of M. catarrhalis in comparison with S. aureus. Despite an increased phosphatidyl serine translocation as revealed by Annexin V binding in flow cytometry analyses, neither M. catarrhalis nor S. aureus induced activation-associated apoptotic cell death in purified human tonsillar B cells. In contrast, a vigorous B cell proliferation, as quantified using thymidine incorporation and CFSE staining, was observed. An increased expression of an array of surface proteins (i.e., CD19, CD21, CD40, CD45, CD54, CD69, CD86, CD95, and HLA-DR) and IgM production was found upon activation with M. catarrhalis. In conclusion, M. catarrhalis-dependent B cell activation does not result in apoptosis but in cell division and nonspecific IgM synthesis, suggesting that the bacterial interaction with tonsillar B cells serves to redirect the early adaptive immune response.

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Characterization of the IgD Binding Site of Encapsulated Haemophilus influenzae Serotype b

Cited by 11 publications

References 30 publications

Molecular Aspects ofMoraxella catarrhalisPathogenesis

Molecular Aspects ofMoraxella catarrhalisPathogenesis

Paediatric nodal marginal zone B‐cell lymphadenopathy of the neck: a Haemophilus influenzae‐driven immune disorder?

Moraxella catarrhalis-dependent tonsillar B cell activation does not lead to apoptosis but to vigorous proliferation resulting in nonspecific IgM production

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