Sequence changes at the V-D junction of the VH1 heavy chain of anti-phosphocholine antibodies alter binding to and protection against Streptococcus pneumoniae

International Immunology
W X GuoJ J Kenny

Abstract

X-linked immune deficient (Xid) mice fail to produce anti-phosphocholine (PC) antibodies even after immunization with Streptococcus pneumoniae. Consequently, Xid mice are extremely susceptible to infection with S. pneumoniae, PC-specific B cells appear to undergo clonal deletion in Xid mice; however, a new thymus-dependent form of PC, 6-(O-phosphocholine)hydroxyhexanoate (EPC), can rescue PC-specific B cells from the bone marrow presumably by providing T cell help before clonal deletion. Analysis of PC-specific IgG hybridomas from Xid mice revealed utilization of several V-D junctional variants of the VH1 gene segment rearranged to different D and JH gene segments. The majority of Xid anti-PC antibodies exhibit an Asp-->Gly95H replacement at the V-D junction. These Gly95H VH1 variants associate with kappa 1C L chains to produce anti-PC antibodies that: (1) have low relative affinity for PC, (ii) are heteroclitic for nitrophenylphosphocholine and (iii) fall to bind to or provide protection against S. pneumoniae. Single prototypic V-D variants of the T15 idiotype (Asp95H), M603 idiotype (Asn95H) and M167 idiotype (Asp95H-Ala96H) were also induced in Xid mice. The M603-like and M167-like antibodies bound to and protected against S...Continue Reading

Citations

Dec 8, 2004·The Journal of Experimental Medicine·Mi-Kyung ChangJoseph L Witztum
May 29, 1998·Immunological Reviews·G D WiensM B Rittenberg
Nov 12, 2010·Clinical and Vaccine Immunology : CVI·Masahide Yano, Liise-anne Pirofski
May 17, 2000·Proceedings of the National Academy of Sciences of the United States of America·Q S MiJ J Kenny
Jun 9, 2005·European Journal of Immunology·Peter M Dammers, Frans G M Kroese
May 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yifang ChenGregg J Silverman
Feb 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J J KennyD L Longo
Jan 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lina HuJames J Kenny
May 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gregory D WiensMarvin B Rittenberg

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacterial Pneumonia

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.

Antiphospholipid Syndrome

Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by the presence of antibodies directed against phospholipids.

Bacterial Pneumonia (ASM)

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.