Protein D, an immunoglobulin D-binding protein of Haemophilus influenzae: cloning, nucleotide sequence, and expression in Escherichia coli

Janson, Håkan; Hedén, Lars-Olof; Grubb, Anders; Ruan, Maorong; Forsgren, Arne

doi:10.1128/iai.59.1.119-125.1991

Cited by 70 publications

(62 citation statements)

References 52 publications

(27 reference statements)

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“…Flow cytometry was also used when analyzing the specificity of the antibodies produced after M. catarrhalisinduced B cell stimulation. A panel of normal respiratory pathogens, i.e., M. catarrhalis strains BBH18 and RH4, Haemophilus influenzae strain NTHi772 [34], and Streptococcus pneumoniae strain TIGR 4 [35], was tested separately for antibody binding (IgM, IgD, IgA, IgG, and IgE) after 1 h incubation on ice with cell-free supernatants from B cells activated with M. catarrhalis.…”

Section: Flow Cytometry Analysesmentioning

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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Section: Flow Cytometry Analysesmentioning

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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“…Such recombination could remove a major part of S^i and the Cn loci, leading to tlieir slgM'IgD"^ phenotype and poor ability to undergo furtber isotype switch. This deletion event and extensive somatic mutation may be triggered through the engagement of sIgD by bacterial antigens, such as tbe IgD-binding protein D from Haemophilus infltienzae B (36) or by Fc8 receptors of T-belper cells, a T-cell subset known to enhance humoral immune responses (37). Recent experiments suggest that triggering sIgD only or sIgD together with sIgM may result in different effects on B cells, as sIgM but not sIgD is associated with prohibitin and a prohibitin-related protein tbat transduces negative cellular signals (38).…”

Section: Cyl-cb Switchmentioning

confidence: 99%

Germinal center development

Liu¹,

Arpin²

1997

Immunological Reviews

327

228

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Using a set of surface markers including IgD and CD38, human tonsillar B cells were classified into discrete subpopulations. Molecular and functional analysis allowed us to identify: i) two sets of naive B cells (Bm1 and Bm2); ii) germinal center founder cells (Bm2'); iii) an obscure population of germinal center B cells, displaying a high load of somatic mutations in IgV genes, C mu to C delta switch and preferential Ig lambda light chain usage: these cells may represent the precursors of normal and malignant IgD-secreting plasma cells; iv) the centroblasts (Bm3) in which somatic mutation machinery is activated; v) the centrocytes (Bm4) in which isotype switch occurs; vi) the memory B cells. The characterization of these subpopulations showed that: i) programmed cell death is set before somatic mutations, possibly providing an efficient way for affinity maturation; ii) only high affinity centrocytes are allowed to switch isotype; iii) CD40-ligation inhibits plasmacytic differentiation of mature B lymphocytes; iv) memory B cells preferentially differentiate into plasma cells; v) IgD isotype switch occurs in normal B cells; vi) receptor editing may be induced by somatic mutations in germinal centers. We also characterized two types of antigen-presenting cells in germinal centers: follicular dendritic cells that select high affinity B cells, and a new subset of germinal center dendritic cells that activate germinal center T cells.

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“…This observation may suggest a Th2 dominance in the response to immunization with EF-Tu, but needs further verification. Our results collectively suggest that EF-Tu may be included in a multicomponent vaccine together with other immunogenic proteins such as Protein D [33] and Protein F [10,34]. However, the close homology in EF-Tu derived from different bacterial species poses a potential threat to the normal flora (microbiota).…”

Section: Discussionmentioning

confidence: 73%

“…Following the addition of 0.5 μg of purified recombinant EF-Tu, Protein D [33], or Protein F [9] www.eji-journal.eu BSA per well. After washing, the samples were incubated for 1 h at RT with sera diluted 1:100 in PBST with 2.5% BSA and subsequently washed three times.…”

Section: Enzyme Linked Immunosorbent Assay (Elisa)mentioning

confidence: 99%

Anti‐EF‐Tu IgG titers increase with age and may contribute to protection against the respiratory pathogen Haemophilus influenzae

Thofte

Kaur

et al. 2019

Eur J Immunol

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Non‐typeable Haemophilus influenzae (NTHi) is a pathogen that commonly colonizes the nasopharynx of preschool children, causing opportunistic infections including acute otitis media (AOM). Patients suffering from chronic obstructive pulmonary disease (COPD) are persistently colonized with NTHi and occasionally suffer from exacerbations by the bacterium leading to increased morbidity. Elongation‐factor thermo unstable (EF‐Tu), a protein critical for bacterial protein synthesis, has been found to moonlight on the surface of several bacteria. Here, we show that antibodies against NTHi EF‐Tu were present in children already at 18 months of age, and that the IgG antibody titers increased with age. Children harboring NTHi in the nasopharynx also displayed significantly higher IgG concentrations. Interestingly, children suffering from AOM had significantly higher anti‐EF‐Tu IgG levels when NTHi was the causative agent. Human sera recognized mainly the central and C‐terminal part of the EF‐Tu molecule and peptide‐based epitope mapping confirmed similar binding patterns for sera from humans and immunized mice. Immunization of BALB/c and otitis‐prone Junbo (C3H/HeH) mice promoted lower infection rates in the nasopharynx and middle ear, respectively. In conclusion, our results suggest that IgG directed against NTHi EF‐Tu may play an important role in the host immune response against NTHi.

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Protein D, an immunoglobulin D-binding protein of Haemophilus influenzae: cloning, nucleotide sequence, and expression in Escherichia coli

Abstract: The gene for protein D, a membrane-associated protein with specific affinity for human immunoglobulin D, was cloned from a nontypeable strain of Haemophilus influenzae. The gene was expressed in Escherichia coli

Cited by 70 publications

References 52 publications

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

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

Germinal center development

Anti‐EF‐Tu IgG titers increase with age and may contribute to protection against the respiratory pathogen Haemophilus influenzae

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