scholarly journals Molecular and Idiotypic Analyses of the Antibody Response to Cryptococcus neoformansGlucuronoxylomannan-Protein Conjugate Vaccine in Autoimmune and Nonautoimmune Mice

1999 ◽  
Vol 67 (9) ◽  
pp. 4469-4476 ◽  
Author(s):  
Gabriel Nussbaum ◽  
Sharmila Anandasabapathy ◽  
Jean Mukherjee ◽  
Manxia Fan ◽  
Arturo Casadevall ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Antibody Response ◽  
Serum Antibody ◽  
Variable Region ◽  
Relative Magnitude ◽  
Immunoglobulin M ◽  
Mouse Strains ◽  
Immunodominant Antigen ◽  
V Region ◽  
Region Usage

ABSTRACT The antibody response to Cryptococcus neoformanscapsular glucuronoxylomannan (GXM) in BALB/c mice frequently expresses the 2H1 idiotype (Id) and is restricted in variable gene usage. This study examined the immunogenicity of GXM-protein conjugates, V (variable)-region usage, and 2H1 Id expression in seven mouse strains: BALB/c, C57BL/6, A/J, C3H, NZB, NZW, and (NZB × NZW)F1 (NZB/W). All mouse strains responded to vaccination with GXM conjugated to tetanus toxoid (TT), the relative magnitude of the antibody response being BALB/c ∼ C3H > C57BL/6 ∼ NZB ∼ NZW ∼ NZB/W > A/J. Analysis of serum antibody responses to GXM with polyclonal and monoclonal antibodies to the 2H1 Id revealed significant inter- and intrastrain differences in idiotype expression. Thirteen monoclonal antibodies (MAbs) (two immunoglobulin M [IgM], three IgG3, one IgG1, three IgG2a, two IgG2b, and two IgA) to GXM were generated from one NZB/W mouse and one C3H/He mouse. The MAbs from the NZB/W mouse were all 2H1 Id positive (Id+) and structurally similar to those previously generated in BALB/c mice, including the usage of a VH from the 7183 family and Vκ5.1. Administration of both 2H1 Id+and Id− MAbs from NZB/W and C3H/H3 mice prolonged survival in a mouse model of cryptococcosis. Our results demonstrate (i) that V-region restriction as indicated by the 2H1 Id is a feature of both primary and secondary responses of several mouse strains; and (ii) that there is conservation of V-region usage and length of the third complementarity-determining region in antibodies from three mouse strains. The results suggest that V-region restriction is a result of antibody structural requirements necessary for binding an immunodominant antigen in GXM.

scholarly journals In Vitro and In Vivo Neutralization of the Relapsing Fever Agent Borrelia hermsii with Serotype-Specific Immunoglobulin M Antibodies

2001 ◽  
Vol 69 (2) ◽  
pp. 1009-1015 ◽  
Author(s):  
Alan G. Barbour ◽  
Virgilio Bundoc
Keyword(s):  
Monoclonal Antibodies ◽  
Antibody Response ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Relapsing Fever ◽  
Borrelia Hermsii ◽  
Intact Cells ◽  
Whole Cells

ABSTRACT The antigenic variation of the relapsing fever agent Borrelia hermsii is associated with changes in the expression of the Vlp and Vsp outer membrane lipoproteins. To investigate whether these serotype-defining proteins are the target of a neutralizing and protective antibody response, monoclonal antibodies were produced from spleens of infected mice just after clearance of serotype 7 cells from the blood. Two immunoglobulin M monoclonal antibodies, H7-7 and H7-12, were studied in detail. Both antibodies specifically agglutinated serotype 7 cells and inhibited their growth in vitro. Administered to mice before or after infection, both antibodies provided protection against infection or substantially reduced the number of spirochetes in the blood of mice after infection. Whereas antibody H7-12 bound to Vlp7 in Western blotting, enzyme-linked immunosorbent assay, and immunoprecipitation assays, as well as to whole cells in other immunoassays, antibody H7-7 only bound to wet, intact cells of serotype 7. Antibody H7-7 selected against cells expressing Vlp7 in vitro and in vivo, an indication that Vlp7 was a conformation-sensitive antigen for the antibody. Vaccination of mice with recombinant Vlp7 with adjuvant elicited antibodies that bound to fixed whole cells of serotype 7 and to Vlp7 in Western blots, but these antibodies did not inhibit the growth of serotype 7 in vitro and did not provide protection against an infectious challenge with serotype 7. The study established that a Vlp protein was the target of a neutralizing antibody response, and it also indicated that the conformation and/or the native topology of Vlp were important for eliciting that immunity.

scholarly journals Both Th1 and Th2 Cytokines Affect the Ability of Monoclonal Antibodies To Protect Mice against Cryptococcus neoformans

2001 ◽  
Vol 69 (10) ◽  
pp. 6445-6455 ◽  
Author(s):  
David O. Beenhouwer ◽  
Scott Shapiro ◽  
Marta Feldmesser ◽  
Arturo Casadevall ◽  
Matthew D. Scharff
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
Cryptococcus Neoformans ◽  
Capsular Polysaccharide ◽  
Variable Region ◽  
Interleukin 12 ◽  
Mouse Strains ◽  
Natural Immunity ◽  
Cryptococcal Infection ◽  
Th1 And Th2

ABSTRACT Variable-region-identical mouse immunoglobulin G1 (IgG1), IgG2b, and IgG2a monoclonal antibodies to the capsular polysaccharide ofCryptococcus neoformans prolong the lives of mice infected with this fungus, while IgG3 is either not protective or enhances infection. CD4+ T cells are required for IgG1-mediated protection, and CD8+ T cells are required for IgG3-mediated enhancement. Gamma interferon is required for both effects. These findings revealed that T cells and cytokines play a role in the modulation of cryptococcal infection by antibodies and suggested that it was important to more fully define the cytokine requirements of each of the antibody isotypes. We therefore investigated the efficacy of passively administered variable-region-identical IgG1, IgG2a, IgG2b, and IgG3 monoclonal antibodies against intravenous infection withC. neoformans in mice genetically deficient in interleukin-12 (IL-12), IL-6, IL-4, or IL-10, as well as in the parental C57BL/6J strain. The relative inherent susceptibilities of these mouse strains to C. neoformans were as follows: IL-12−/− > IL-6−/− > C57BL/6J ≈ IL-4−/− ≫ IL-10−/−. This is consistent with the notion that a Th1 response is necessary for natural immunity against cryptococcal infection. However, none of the IgG isotypes prolonged survival in IL-12−/−, IL-6−/−, or IL-4−/− mice, and all isotypes significantly enhanced infection in IL-10−/− mice. These results indicate that passive antibody-mediated protection againstC. neoformans requires both Th1- and Th2-associated cytokines and reveal the complexity of the mechanisms through which antibodies modulate infection with this organism.

scholarly journals Dominant Epitopes of the C6 Diagnostic Peptide of Borrelia burgdorferi Are Largely Inaccessible to Antibody on the Parent VlsE Molecule

2007 ◽  
Vol 14 (8) ◽  
pp. 931-936 ◽  
Author(s):  
Monica E. Embers ◽  
Mary B. Jacobs ◽  
Barbara J. B. Johnson ◽  
Mario T. Philipp
Keyword(s):  
Antibody Response ◽  
Variable Region ◽  
Immunoglobulin M ◽  
Antibody Responses ◽  
Full Length ◽  
Molecular Surface ◽  
Surface Molecule ◽  
Igg Antibodies ◽  
Specific Antibodies ◽  
Variable Surface

ABSTRACTLyme borreliosis (LB) is a disease for which antibody-based detection assays are often required for diagnosis. The variable surface molecule VlsE and IR6, one of its invariable regions, are commonly targeted by the antibody response in infected individuals. A series of enzyme-linked immunosorbent assays was performed to comparatively examine the antibody responses of North American LB patients (n= 37) to VlsE and invariable segments of this molecule. Both immunoglobulin M (IgM) and IgG responses to full-length VlsE and to peptides reproducing invariable regions 2, 4, and 6, as well as the invariable domains at the amino and carboxyl termini of VlsE, were assessed. The proportions and specificities of reactivity to the invariable segments were tested by using cognate peptides as competitors for VlsE binding by patient serum antibodies. IR6 epitopes (by the C6 peptide) were found to dominate the response to invariable segments. IR6 (C6)-specific antibodies were detected in 78% of the serum specimens, whereas <40% of patients generated antibodies that bound the N- or C-terminal domain and <12% of patients responded to either IR2 or IR4. Interestingly, 15 of 37 patients generated IgG antibodies that reacted with C6 but not with VlsE. Conversely, IgM responses were frequent for VlsE but not for invariable segments. A representative number of the serum specimens (n= 8) that contained IgG antibodies reacting with both C6 and VlsE was assessed in competition experiments, using C6 as a competitor. Only half of these specimens contained IgG antibodies whose binding to VlsE could be inhibited >50% by competition with the added C6 peptide. The median percent inhibition was 45.5%. These findings indicate that IR6 epitopes are largely concealed from the VlsE molecular surface and that full-length VlsE-based diagnosis likely detects antibodies to conformational and/or variable region epitopes.

scholarly journals The monoclonal anti-phosphorylcholine antibody response in several murine strains: genetic implications of a diverse repertoire.

1977 ◽  
Vol 145 (4) ◽  
pp. 876-891 ◽  
Author(s):  
P J Gearhart ◽  
N H Sigal ◽  
N R Klinman
Keyword(s):  
Monoclonal Antibodies ◽  
Antibody Response ◽  
B Cell ◽  
Variable Region ◽  
Cross Reactivity ◽  
Antibody Specificity ◽  
Cell Repertoire ◽  
Remarkable Similarity ◽  
B Cell Repertoire ◽  
Structural Relationships

The idiotypic identification of monoclonal antibodies has been used to define and enumerate clonotypes within the murine repertoire of B cells specific for phosphorylcholine (PC). The response in the BALB/c strain is dominated by a single antibody specificity which is identical to TEPC 15 protein; however, antibody without the TEPC 15 idiotype appears heterogeneous by idiotypic cross-reactivity and hapten inhibition of binding to antigen. Dissection of the PC-specific repertoire in the AKR, A/He, and C3H strains has indicated that some monoclonal antibodies share binding-site idiotypic determinants with TEPC 15, although these clones represent a minority of the precursor cells. In addition to providing insights into the heterogeneity and expression of the murine B-cell repertoire, these studies emphasize structural relationships between PC-specific clonotypes. Within the BALB/c strain, some antibodies share combining-site-related idiotypic specificities with TEPC 15, but differ in other variable region determinants. Among allotypically distinct strains, there exists a remarkable similarity of variable region determinants in at least a minority of antibodies.

scholarly journals Modulation of Antibody-Mediated Immune Response by Probiotics in Chickens

2005 ◽  
Vol 12 (12) ◽  
pp. 1387-1392 ◽  
Author(s):  
Hamid R. Haghighi ◽  
Jianhua Gong ◽  
Carlton L. Gyles ◽  
M. Anthony Hayes ◽  
Babak Sanei ◽  
...  
Keyword(s):  
Antibody Response ◽  
Serum Antibody ◽  
Bifidobacterium Bifidum ◽  
Immunoglobulin M ◽  
Antibody Responses ◽  
Gut Contents ◽  
Igg Antibody ◽  
Mucosal Antibody ◽  
Probiotic Product ◽  
Phosphate Buffered Saline

ABSTRACT Probiotic bacteria, including Lactobacillus acidophilus and Bifidobacterium bifidum, have been shown to enhance antibody responses in mammals. The objective of this study was to examine the effects of a probiotic product containing the above bacteria in addition to Streptococcus faecalis on the induction of the chicken antibody response to various antigens, both systemically and in the gut. The birds received probiotics via oral gavage and subsequently were immunized with sheep red blood cells (SRBC) and bovine serum albumin (BSA) to evaluate antibody responses in serum or with tetanus toxoid (TT) to measure the mucosal antibody response in gut contents. Control groups received phosphate-buffered saline. Overall, BSA and SRBC induced a detectable antibody response as early as week 1 postimmunization (p.i.), which lasted until week 3 p.i. Probiotic-treated birds had significantly (P ≤ 0.001) more serum antibody (predominantly immunoglobulin M [IgM]) to SRBC than the birds that were not treated with probiotics. However, treatment with probiotics did not enhance the serum IgM and IgG antibody responses to BSA. Immunization with TT resulted in the presence of specific IgA and IgG antibody responses in the gut. Again, treatment with probiotics did not change the level or duration of the antibody response in the gut. In conclusion, probiotics enhance the systemic antibody response to some antigens in chickens, but it remains to be seen whether probiotics have an effect on the generation of the mucosal antibody response.

scholarly journals Serum antibody response in COVID-19-recovered patients who retested positive

2021 ◽  
Vol 47 (04) ◽  
pp. 195-201
Author(s):  
Nicole Atchessi ◽  
Megan Striha ◽  
Rojiemiahd Edjoc ◽  
Christine Abalos ◽  
Amanda Lien ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Antibody Response ◽  
Reverse Transcription ◽  
False Negative ◽  
Serum Antibody ◽  
Immunoglobulin M ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Antibody Levels

Background: Research studies comparing antibody response from coronavirus disease 2019 (COVID-19) cases that retested positive (RP) using reverse transcription polymerase chain reaction (RT-PCR) and those who did not retest positive (NRP) were used to investigate a possible relationship between antibody response and retesting status. Methods: Seven data bases were searched. Research criteria included cohort and case-control studies, carried out worldwide and published before September 9, 2020, that compared the serum antibody levels of hospitalized COVID-19 cases that RP after discharge to those that did NRP. Results: There is some evidence that immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody levels in RP cases were lower compared with NRP cases. The hypothesis of incomplete clearance aligns with these findings. The possibility of false negative reverse transcription polymerase chain reaction (RT-PCR) test results during viral clearance is also plausible, as concentration of the viral ribonucleic acid (RNA) in nasopharyngeal and fecal swabs fluctuate below the limits of RT-PCR detection during virus clearance. The probability of reinfection was less likely to be the cause of retesting positive because of the low risk of exposure where cases observed a 14 day-quarantine after discharge. Conclusion: More studies are needed to better explain the immune response of recovered COVID-19 cases retesting positive after discharge.

scholarly journals Improved Survival of Mice Deficient in Secretory Immunoglobulin M following Systemic Infection with Cryptococcus neoformans

2009 ◽  
Vol 78 (1) ◽  
pp. 441-452 ◽  
Author(s):  
Krishanthi S. Subramaniam ◽  
Kausik Datta ◽  
Matthew S. Marks ◽  
Liise-anne Pirofski
Keyword(s):  
T Cell ◽  
B Cells ◽  
Cryptococcus Neoformans ◽  
Serum Antibody ◽  
Immunoglobulin M ◽  
T Cell Subsets ◽  
Mouse Strains ◽  
Proinflammatory Mediators ◽  
Cell Immunity ◽  
Increased Risk

ABSTRACT Cryptococcus neoformans causes severe, and often fatal, disease (cryptococcosis) in immunocompromised patients, particularly in those with HIV/AIDS. Although resistance to cryptococcosis requires intact T-cell immunity, a possible role for antibody/B cells in protection against natural disease has not been definitively established. Previous studies of the antibody response to the C. neoformans capsular polysaccharide glucuronoxylomannan (GXM) have demonstrated that patients who are at increased risk for cryptococcosis have lower serum levels of GXM-reactive IgM than those who are not at risk, leading to the hypothesis that IgM might contribute to resistance to cryptococcosis. To determine the influence of IgM on susceptibility to systemic cryptococcosis in a murine model, we compared the survival of mice deficient in serum IgM (secretory IgM deficient [sIgM−/−]) and C57BL/6 × 129Sv (control) mice after intraperitoneal infection with C. neoformans strain 24067 and analyzed the splenic B- and T-cell subsets by flow cytometry and the serum and splenic cytokine/chemokine and serum antibody profiles of each mouse strain. The results showed that sIgM−/− mice survived significantly longer than control mice when challenged with 105 CFU of C. neoformans 24067. Naïve sIgM−/− mice had higher levels of B-1 (CD5+) B cells, proinflammatory mediators (interleukin-6 [IL-6], IL-1β, MIP-1β, tumor necrosis factor alpha [TNF-α], and gamma interferon [IFN-γ]), and anti-inflammatory mediators (IL-10 and IL-13) and significantly higher titers of GXM-specific IgG2a 3 weeks postinfection. In addition, CD5+ splenocytes from both mouse strains had fungicidal activity against C. neoformans. Taken together, these results suggest that the inflammatory milieu in sIgM−/− mice might confer enhanced resistance to systemic cryptococcosis, stemming in part from the antifungal activity of B-1 B cells.

scholarly journals Specific Intracellular Adhesion Molecule-Grabbing Nonintegrin R1 Is Not Involved in the Murine Antibody Response to Pneumococcal Polysaccharides

2007 ◽  
Vol 75 (12) ◽  
pp. 5748-5752 ◽  
Author(s):  
Leen Moens ◽  
Axel Jeurissen ◽  
Greet Wuyts ◽  
Padraic G. Fallon ◽  
Boon Louis ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Antibody Response ◽  
Adhesion Molecule ◽  
Antibody Production ◽  
Knockout Mice ◽  
Immunoglobulin M ◽  
Wild Type ◽  
Igg Antibody ◽  
Igm Antibody ◽  
Intracellular Adhesion Molecule

ABSTRACT Streptococcus pneumoniae is a microorganism that frequently causes serious infections in children, the elderly, and immunocompromised patients. We studied whether the specific intracellular adhesion molecule-grabbing nonintegrin R1 (Sign-R1) receptor, involved in the uptake of capsular polysaccharides (caps-PS) by antigen-presenting cells, is necessary for the antibody response to pneumococcal caps-PS and phosphorylcholine (PC). The antibody response to caps-PS and PC was evaluated after vaccination with soluble caps-PS (Pneumovax) and after vaccination with heat-killed S. pneumoniae. The role of Sign-R1 was investigated by using Sign-R1 knockout mice and anti-Sign-R1 monoclonal antibodies. The immunoglobulin M (IgM) and IgG antibody response to PC and caps-PS (serotypes 3 and 14) was not affected by anti-Sign-R1 monoclonal antibodies. The IgM antibody response in Sign-R1 knockout mice was comparable to the antibody response in wild-type mice. The IgG antibody response to serotype 3, but not to serotype 14, tended to be lower in Sign-R1 knockout mice compared to wild-type mice. In conclusion, we found that Sign-R1 is not involved in the IgM antibody production to PC and caps-PS serotype 3 or 14 and the IgG immune response to PC and caps-PS serotype 14. There is no direct relation between capture and uptake of caps-PS serotype 14 by Sign-R1 and the initiation of the anti-caps-PS antibody production in mice.

scholarly journals IGVL gene region usage correlates with distinct clinical presentation in IgM vs non-IgM light chain amyloidosis

2021 ◽  
Vol 5 (8) ◽  
pp. 2101-2105
Author(s):  
Surbhi Sidana ◽  
Surendra Dasari ◽  
Taxiarchis V. Kourelis ◽  
Angela Dispenzieri ◽  
David L. Murray ◽  
...  
Keyword(s):  
Light Chain ◽  
Clinical Presentation ◽  
Variable Region ◽  
Immunoglobulin M ◽  
Al Amyloidosis ◽  
Amyloid Deposits ◽  
Peripheral Nerve Involvement ◽  
Gene Usage ◽  
Region Usage ◽  
Organ Tropism

Abstract Patients with immunoglobulin M (IgM) light chain (AL) amyloidosis have a distinct clinical presentation compared with those with non-IgM amyloidosis. We hypothesized that differential immunoglobulin light-chain variable region (IGVL) gene usage may explain the differences in organ involvement, because IGVL usage correlates with organ tropism. IGVL usage was evaluated by mass spectrometry of amyloid deposits (IgM, n = 45; non-IgM, n = 391) and differed across the 2 groups. In the λ family, LV2-08 (13% vs 2%; P &lt; .001) and LV2-14 (36% vs 10%; P &lt; .001) usage was more common in IgM vs non-IgM amyloidosis, whereas LV1-44 (0% vs 10%; P = .02) and LV6-57 (2% vs 18%; P = .004) usage was less common. In the κ family, there was a trend toward higher KV4-01 (11% vs 4%; P = .06) usage in IgM amyloidosis. IGVL usage correlated with disease characteristics/organ tropism. LV2-14 (more common in IgM amyloidosis) has historically been associated with peripheral nerve involvement and lower light chain burden, which were more frequent in IgM amyloidosis. LV1-44 (less common in IgM), associated with cardiac involvement, was less frequent in IgM patients. LV6-57 (less common in IgM) is associated with t(11;14), which was less frequent in IgM patients. In conclusion, IGVL gene usage differs in patients with IgM vs non-IgM amyloidosis and may explain the distinct clinical presentation.

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