... 1893 Nicolaas A. BosoV, Cornelia G. MeeuwsenO, Elisabeth De Glopper-Van der Veero, Theodoor W... more ... 1893 Nicolaas A. BosoV, Cornelia G. MeeuwsenO, Elisabeth De Glopper-Van der Veero, Theodoor W. Van den AkkerO, Jiri Radl*, Kornelisje A. Zwaagstra. and Robbed BennerO ... It may be that the Ly-1 B cell lineage is involved in BMG. ...
Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasm... more Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasma cells in the bone marrow, secreting monoclonal (M) paraprotein. MGUS is associated with increased susceptibility to infections, which may reflect altered B-cell repertoire. To investigate this, we examined the IgM, IgG and IgA B-cell repertoire diversity in MGUS at baseline and after influenza vaccination (n=16) in comparison to healthy controls (HCs) (n=16). The CDR3 region of the immunoglobulin heavy chain variable (IGHV) region gene was amplified and B-cell spectratypes analyzed by high-resolution electrophoresis. Spectratype Gaussian distribution, kurtosis and skewness were quantified to measure repertoire shifts. Both HC and MGUS baseline spectratypes show inter-individual variability that is more pronounced in the IGHG and IGHA repertoires. Overall, baseline B cell repertoire is more altered in MGUS, with oligoclonality observed in 50% (p=0.01). Post-vaccination, significant diff...
We used Listeria monocytogenes, a gram-positive, facultative intracellular bacterium, to study th... more We used Listeria monocytogenes, a gram-positive, facultative intracellular bacterium, to study the gut mucosal immune responses following oral infection. We employed a germfree (GF) mouse model to try to accentuate the development of a humoral mucosal immune response in the gut, and we used oral colonization with one of the mutants, actA-negative (DeltaactA) L. monocytogenes, to restrict infection largely to the gut. The DeltaactA mutant was able to colonize the intestinal mucosa of formerly GF mice for long periods of time without causing disease while eliciting secretory immunoglobulin A (IgA) responses, as evidenced by gut tissue fragment culture assays. Flow cytometric analyses and immunohistochemical methods showed the development of only minimal germinal center reactions (GCR) in Peyer's patches and more robust GCR in mesenteric lymph nodes. Pronounced increases in total (natural) IgA production occurred in gut tissues by day 7 and were maintained for up to 90 days. Levels of specific IgA were modest in gut tissues on day 14, increased until day 76, and stabilized at day 90. We also observed a significant rise in serum IgA and IgG1 levels following oral infection by listeriae. Upon colonization, the organisms mainly infected the intestines and intestinal lumen, and we only sporadically observed few colony-forming bacteria in the liver and spleen. We observed a marked rise in IgA-secreting cells, including listeria-specific IgA antibody-secreting cells, in the lamina propria of the small intestine by enzyme-linked immunospot assays. To ascertain whether some of the IgA was specific for listeriae, we performed Western blot analysis to test the reactivity of IgA from fragment cultures to antigens in sonicates of L. monocytogenes. We detected IgA binding to antigenic proteins with molecular masses of 96, 60, 40, and 14 kDa in the Listeria sonicates.
Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasm... more Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasma cells in the bone marrow, secreting monoclonal (M) paraprotein. MGUS is associated with increased susceptibility to infections, which may reflect altered B-cell repertoire. To investigate this, we examined the IgM, IgG and IgA B-cell repertoire diversity in MGUS at baseline and after influenza vaccination (n=16) in comparison to healthy controls (HCs) (n=16). The CDR3 region of the immunoglobulin heavy chain variable (IGHV) region gene was amplified and B-cell spectratypes analyzed by high-resolution electrophoresis. Spectratype Gaussian distribution, kurtosis and skewness were quantified to measure repertoire shifts. Both HC and MGUS baseline spectratypes show inter-individual variability that is more pronounced in the IGHG and IGHA repertoires. Overall, baseline B cell repertoire is more altered in MGUS, with oligoclonality observed in 50% (p=0.01). Post-vaccination, significant diff...
... 1893 Nicolaas A. BosoV, Cornelia G. MeeuwsenO, Elisabeth De Glopper-Van der Veero, Theodoor W... more ... 1893 Nicolaas A. BosoV, Cornelia G. MeeuwsenO, Elisabeth De Glopper-Van der Veero, Theodoor W. Van den AkkerO, Jiri Radl*, Kornelisje A. Zwaagstra. and Robbed BennerO ... It may be that the Ly-1 B cell lineage is involved in BMG. ...
Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasm... more Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasma cells in the bone marrow, secreting monoclonal (M) paraprotein. MGUS is associated with increased susceptibility to infections, which may reflect altered B-cell repertoire. To investigate this, we examined the IgM, IgG and IgA B-cell repertoire diversity in MGUS at baseline and after influenza vaccination (n=16) in comparison to healthy controls (HCs) (n=16). The CDR3 region of the immunoglobulin heavy chain variable (IGHV) region gene was amplified and B-cell spectratypes analyzed by high-resolution electrophoresis. Spectratype Gaussian distribution, kurtosis and skewness were quantified to measure repertoire shifts. Both HC and MGUS baseline spectratypes show inter-individual variability that is more pronounced in the IGHG and IGHA repertoires. Overall, baseline B cell repertoire is more altered in MGUS, with oligoclonality observed in 50% (p=0.01). Post-vaccination, significant diff...
We used Listeria monocytogenes, a gram-positive, facultative intracellular bacterium, to study th... more We used Listeria monocytogenes, a gram-positive, facultative intracellular bacterium, to study the gut mucosal immune responses following oral infection. We employed a germfree (GF) mouse model to try to accentuate the development of a humoral mucosal immune response in the gut, and we used oral colonization with one of the mutants, actA-negative (DeltaactA) L. monocytogenes, to restrict infection largely to the gut. The DeltaactA mutant was able to colonize the intestinal mucosa of formerly GF mice for long periods of time without causing disease while eliciting secretory immunoglobulin A (IgA) responses, as evidenced by gut tissue fragment culture assays. Flow cytometric analyses and immunohistochemical methods showed the development of only minimal germinal center reactions (GCR) in Peyer's patches and more robust GCR in mesenteric lymph nodes. Pronounced increases in total (natural) IgA production occurred in gut tissues by day 7 and were maintained for up to 90 days. Levels of specific IgA were modest in gut tissues on day 14, increased until day 76, and stabilized at day 90. We also observed a significant rise in serum IgA and IgG1 levels following oral infection by listeriae. Upon colonization, the organisms mainly infected the intestines and intestinal lumen, and we only sporadically observed few colony-forming bacteria in the liver and spleen. We observed a marked rise in IgA-secreting cells, including listeria-specific IgA antibody-secreting cells, in the lamina propria of the small intestine by enzyme-linked immunospot assays. To ascertain whether some of the IgA was specific for listeriae, we performed Western blot analysis to test the reactivity of IgA from fragment cultures to antigens in sonicates of L. monocytogenes. We detected IgA binding to antigenic proteins with molecular masses of 96, 60, 40, and 14 kDa in the Listeria sonicates.
Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasm... more Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasma cells in the bone marrow, secreting monoclonal (M) paraprotein. MGUS is associated with increased susceptibility to infections, which may reflect altered B-cell repertoire. To investigate this, we examined the IgM, IgG and IgA B-cell repertoire diversity in MGUS at baseline and after influenza vaccination (n=16) in comparison to healthy controls (HCs) (n=16). The CDR3 region of the immunoglobulin heavy chain variable (IGHV) region gene was amplified and B-cell spectratypes analyzed by high-resolution electrophoresis. Spectratype Gaussian distribution, kurtosis and skewness were quantified to measure repertoire shifts. Both HC and MGUS baseline spectratypes show inter-individual variability that is more pronounced in the IGHG and IGHA repertoires. Overall, baseline B cell repertoire is more altered in MGUS, with oligoclonality observed in 50% (p=0.01). Post-vaccination, significant diff...
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