Further Experimental Studies on the Prevention of Rh Haemolytic Disease

Clarke, C. A.; Donohoe, W. T. A.; McConnell, R. B.; Woodrow, J. C.; Finn, Ronald D.; Krevans, Julius R.; Kulke, W.; Lehane, Daniel E.; Sheppard, P. M.

doi:10.1136/bmj.1.5336.979

Cited by 221 publications

(61 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two lines of research support this view. First, Ag-specific IgM, passively administered to mice or humans together with Ag can enhance the Ab response to the Ag via Ab feedback regulation (31)(32)(33)(34)(35). This enhancement depends on the ability of IgM to activate C (34,35).…”

Section: Igm Mutation | Natural Igmmentioning

confidence: 99%

Requirement for complement in antibody responses is not explained by the classic pathway activator IgM

Rutemark

Alicot

Bergman

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Animals lacking complement factors C1q, C2, C3, or C4 have severely impaired Ab responses, suggesting a major role for the classic pathway. The classic pathway is primarily initiated by antigen–Ab complexes. Therefore, its role for primary Ab responses seems paradoxical because only low amounts of specific Abs are present in naive animals. A possible explanation could be that the classic pathway is initiated by IgM from naive mice, binding with sufficient avidity to the antigen. To test this hypothesis, a knock-in mouse strain, Cμ13, with a point mutation in the gene encoding the third constant domain of the μ-heavy chain was constructed. These mice produce IgM in which proline in position 436 is substituted with serine, a mutation previously shown to abrogate the ability of mouse IgM to activate complement. Unexpectedly, the Ab response to sheep erythrocytes and keyhole limpet hemocyanin in Cμ13 mice was similar to that in WT mice. Thus, although secreted IgM and the classic pathway activation are both required for the normal primary Ab response, this does not require that IgM activate C. This led us to test Ab responses in animals lacking one of three other endogenous activators of the classic pathway: specific intracellular adhesion molecule-grabbing nonintegrin R1, serum amyloid P component, and C-reactive protein. Ab responses were also normal in these animals.

show abstract

Section: Igm Mutation | Natural Igmmentioning

confidence: 99%

Requirement for complement in antibody responses is not explained by the classic pathway activator IgM

Rutemark

Alicot

Bergman

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…A well-known example of this is the ability of IgG to completely suppress the response to large particulate Ags like erythrocytes (2). The suppressive capacity of IgG is used successfully in the clinic to prevent rhesus D-negative women from becoming immunized against fetal rhesus D-positive erythrocytes transferred via transplacental hemorrhage (3,4). IgG Abs have dual roles in feedback regulation and can also enhance Ab responses.…”

mentioning

confidence: 99%

“…The inhibitory receptor for IgG, Fc␥RIIB, exerts a negative influence on enhancement mediated by IgG1, IgG2a, or IgG2b as demonstrated by the "superenhancement" caused by these isotypes in mice lacking Fc␥RIIB (7,9). IgG enhances not only primary Ab responses, but also secondary Ab responses (10,11), the formation of germinal centers (GCs) 3 (9,12), somatic hypermutation (13), and proliferation of specific CD4 ϩ T cells (9).…”

mentioning

confidence: 99%

A Novel B Cell-Mediated Transport of IgE-Immune Complexes to the Follicle of the Spleen

Hjelm

Karlsson

Heyman

2008

The Journal of Immunology

View full text Add to dashboard Cite

Ag administered i.v. to mice along with specific IgE or IgG2a induces higher Ab- and CD4+ T cell responses than Ag administered alone. The IgE effect is completely dependent on the low-affinity receptor for IgE, CD23, whereas the IgG2a effect depends on activating FcγRs. In vitro studies suggest that IgE/Ag is presented more efficiently than Ag alone to CD4+ T cells by CD23+ B cells and that IgG2a/Ag is presented by FcγR+ dendritic cells (DCs). In this study, we investigate in vivo the early events leading to IgE- and IgG2a-mediated enhancement of immune responses. OVA administered i.v. in PBS in combination with specific IgE binds circulating B cells after 5 min and is found in B cell follicles bound to follicular B cells (CD23high) after 30 min. This novel B cell-dependent route of entry is specific for IgE because IgG2a-Ag complexes were trapped in the marginal zone. OVA-specific CD4+ T cells were found at the T-B border in the T cell zones 12 h after immunization both with IgE/OVA or IgG2a/OVA and proliferated vigorously after 3 days. The findings suggest that IgE- and IgG2a-immune complexes are efficient stimulators of early CD4+ T cell responses and that Ag bound to IgE has a specific route for transportation into follicles.

show abstract

“…A major breakthrough in the management of HDN was the use of passively administered anti-D described by Sir Cyril Clarke in 1963, to prevent anti-Rh D sensitisation (Clarke et al, 1963). The inspiration for this work was the observation that in Rh D incompatible pregnancies where there was also ABO mismatch, any Rh D positive red cells crossing the placenta into the maternal circulation would be rapidly cleared before Rh D sensitisation could occur.…”

Section: Contribution To Haematology and Transfusion Medicinementioning

confidence: 99%

Robin Coombs: his life and contribution to haematology and transfusion medicine

Pamphilon

Scott

2007

Br J Haematol

View full text Add to dashboard Cite

SummaryRobin Coombs was the last survivor of the distinguished group of immunologists that included Philip Gell, John Humphrey, John Marrack, Peter Medawar and Robert White and who were responsible for the renaissance of British Immunology after the Second World War. He is best remembered for describing the antiglobulin test that bears his name. The antiglobulin test revolutionised the diagnosis of haemolytic diseases and the compatibility testing of blood for transfusion. In all, Coombs authored over 200 scientific papers. Haemagglutination reactions became widely used in the diagnosis of a range of infectious agents. Together with Philip Gell, he devised the classification of allergic reactions; these were published in the textbook 'Clinical Aspects of Immunology', which he and Gell first edited in 1963 and which became the leading textbook on medical immunology. Robin Coombs was also one of the founders of the British Society for Immunology.

show abstract

Further Experimental Studies on the Prevention of Rh Haemolytic Disease

Cited by 221 publications

References 5 publications

Requirement for complement in antibody responses is not explained by the classic pathway activator IgM

Requirement for complement in antibody responses is not explained by the classic pathway activator IgM

A Novel B Cell-Mediated Transport of IgE-Immune Complexes to the Follicle of the Spleen

Robin Coombs: his life and contribution to haematology and transfusion medicine

Contact Info

Product

Resources

About