Large numbers of cells in normal mice produce antibody components of isologous erythrocytes

Cunningham, Alastair J.

doi:10.1038/252749a0

Cited by 164 publications

(80 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…18,19 These autoantibodies often cross-react with bacteria or tumor antigens, suggesting their importance in innate immunity. 20,21 It has been demonstrated in an animal model 22 that self-antigen can promote B-cell accumulation and that a significant proportion of natural autoantibodies is the product of this self-antigen-dependent process.…”

Section: Discussionmentioning

confidence: 99%

No Evidence of Autoimmunity in 6-Year-Old Children Immunized at Birth With Recombinant Hepatitis B Vaccine

et al. 2002

View full text Add to dashboard Cite

ABSTRACT. Objectives. Taking into account that genetic predisposition, marked by human leukocyte antigen (HLA) class I and II genes, augments the probability of developing an autoimmune disorder after a triggering vaccination, as largely debated, we investigated the frequency of autoantibody production after recombinant hepatitis B vaccine (rHBv) in 6-year-old children immunized at birth to evaluate an association between autoimmune disorders and hepatitis B virus vaccination.Methods. We investigated the presence of autoantibodies in 210 6-year-old children who were immunized at birth with rHBv: 200 showed anti-hepatitis B surface antigen concentrations >10 mUI/mL at seroconversion (responders), and 10 were nonresponders. Data were compared with those obtained in 109 unvaccinated children. All participants were screened for the presence of antinuclear antibodies (ANAs), anti-DNA, antimitochondrial, anti-liver/kidney microsomal, antireticulin, antismooth muscle (SMA), and antiribosomal antibodies. All participants were also screened for the presence of antithyroid antibodies, such as antithyroglobulin and antiperoxidase, and for antibodies found in type 1 diabetes, such as tyrosine phosphatase (IA-2A) and glutamic acid decarboxylase (GADA). HLA typing was extended to all 10 nonresponders.Results. Autoantibodies were found in 16 of the 200 responders: ANAs were found in 12 (6%), smooth muscle antibodies were found in 4 (2.0%), and antireticulin antibodies and endomysial antibodies were found in 1 girl with ANAs. Antithyroid antibodies, IA-2A, and GADA were not present in any of the participants. No significant difference was found in the frequency of autoantibodies between vaccinated and control children. Three of the 10 nonresponder children were SMA-positive (30% vs 2% of responders); they also carried the supratype HLA-C4AQ0,DRB1*0301,DQB1*02. A family history for autoimmune disorders was present in 3 (18%; 95% confidence interval [CI]: 4.0%-45.6%) of the 16 responder infants with autoantibodies, in 15 (8.4%; 95% CI: 4.6%-13.1%) of responder children without autoantibodies, and in 1 (10%) of the 10 nonsreponder children.Conclusions. From our data, vaccination with rHBv given during the neonatal period does not seem to increase autoantibody production in a 6-year-old children. Autoantibodies, referred to as natural autoantibodies, can be found in healthy participants, but their significance is unclear. These autoantibodies often cross-react with bacteria or tumor antigens, suggesting their importance in innate immunity. It has been demonstrated in an animal model that self-antigen can promote B-cell accumulation, and that a significant proportion of natural autoantibodies is the product of this self-antigen-dependent process. Consequently, it has been speculated that self-antigens play a positive role in recruiting B cells as a part of innate immunity, but this process carries a potential risk for unregulated growth.Spreading of the immune response is a common theme in organ-specific and systemis autoimmune dise...

show abstract

Section: Discussionmentioning

confidence: 99%

No Evidence of Autoimmunity in 6-Year-Old Children Immunized at Birth With Recombinant Hepatitis B Vaccine

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Enrichment in B lymphocytes specific for Br-RBC was performed as described previously (26,29,30). Briefly, nucleated cells from blood of female F 1 FVB/xid mice were separated from RBC on a Lymphoprep (Axis, Oslo, Norway) solution.…”

Section: Rosetting With Bromelain-treated Rbc (Br-rbc)mentioning

confidence: 99%

IL-9-Induced Expansion of B-1b Cells Restores Numbers but Not Function of B-1 Lymphocytes in xid Mice

Knoops

Louahed

Renauld

2004

The Journal of Immunology

View full text Add to dashboard Cite

Mice expressing the X-linked immunodeficiency (xid) mutation lack functional Bruton’s tyrosine kinase and were shown to be specifically deficient in peritoneal B-1 lymphocytes. We have previously shown that IL-9, a cytokine produced by TH2 lymphocytes, promotes B-1 cell expansion in vivo. To determine whether IL-9 overexpression might compensate the xid mutation for B-1 lymphocyte development, we crossed xid mice with IL-9-transgenic mice. In this model, IL-9 restored normal numbers of mature peritoneal B-1 cells that all belonged to the CD5− B-1b subset. Despite this normal B-1 lymphocyte number, IL-9 failed to restore classical functions of B-1 cells, namely, the production of natural IgM Abs, the T15 Id Ab response to phosphorylcholine immunization, and the antipolysaccharide humoral response against Streptococcus pneumoniae. By using bromelain-treated RBC, we showed that the antigenic repertoire of these IL-9-induced B-1b lymphocytes was different from the repertoire of classical CD5+ B-1a cells, indicating that the lack of B-1 function by B-1b cells is associated with distinct Ag specificities. Taken together, our data show that B-1b cell development can restore the peritoneal B-1 population in xid mice but that these B-1b cells are functionally distinct from CD5+ B-1a lymphocytes.

show abstract

“…Anti-PtC is an autoreactive specificity relatively highly represented in the mouse CD5 ϩ B-1 cell subset (2,24,25), is naturally secreted into serum, and is predominantly encoded by either V H 11/V k 9 or V H 12/V k 4/5 (26 -28). Considering its ability to bind to PtC exposed on senescent or bromelain-treated RBC (29,30), anti-PtC autoantibody is presumed to play a role in the clearance of damaged or senescent erythrocytes from the circulation through the action of macrophages (31), which are abundant in red pulp in spleen. As previously shown with V H 11 (32) and V H 12 (33,34) H chain transgenic and with J H locus-targeted V H 12/D H /J H insertion (knockin) mice, genetic provision of rearranged V H 11 (or V H 12) H chain results in an increased, often overwhelming, frequency of anti-PtC CD5 B cell populations during mouse development, resulting in the generation of multiple IgM ϩ B cell subsets, including CD5 ϩ B-1, mature B-2, and marginal zone (MZ) B cells (36) in spleen, all at significant frequencies.…”

mentioning

confidence: 99%

Association of B-1 B Cells with Follicular Dendritic Cells in Spleen

Wen

Shinton

Hardy

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Although CD5+ B-1 B cells have been recognized as an infrequent B cell subset in mice for many years, attempts to identify their histologic location in normal mouse spleen have proven difficult due to both their paucity and low level expression of CD5. In this study we have studied VH11/DH/JH gene-targeted mice, VH11t, that develop elevated numbers of CD5+ VH11/Vk9 B cells with an anti-phosphatidylcholine (anti-PtC) autoreactive specificity, allowing B-1 B cell detection by anti-PtC Id-specific Abs in spleen section staining. Using this approach we found that anti-PtC B-1 cells first appear within the white pulp in neonates, expand in association with follicular dendritic cells (FDC), and localize more centrally than other (non-B-1) IgDhigh follicular B cells in adults. Among neonatal B cells, CD5+ B-1 cells in both normal and VH11t mouse spleen and peritoneal cavity express the highest levels of CXCR5, which is important for FDC development. Injection of purified spleen or peritoneal B-1 cells into RAG knockout mice resulted in B-1 cell follicle formation in spleen, inducing FDC development and plasma cell generation. These results indicate that B-1 B cells are the first B cells to express fully mature levels of CXCR5, thereby promoting the development of FDC.

show abstract

Large numbers of cells in normal mice produce antibody components of isologous erythrocytes

Cited by 164 publications

References 10 publications

No Evidence of Autoimmunity in 6-Year-Old Children Immunized at Birth With Recombinant Hepatitis B Vaccine

No Evidence of Autoimmunity in 6-Year-Old Children Immunized at Birth With Recombinant Hepatitis B Vaccine

IL-9-Induced Expansion of B-1b Cells Restores Numbers but Not Function of B-1 Lymphocytes in xid Mice

Association of B-1 B Cells with Follicular Dendritic Cells in Spleen

Contact Info

Product

Resources

About