Preferential use of lambda light chains is associated with defective mouse antibody responses to the capsular polysaccharide of Neisseria meningitidis group B.
The capsular polysaccharide of Neisseria meningitidis group B (CpsB) is a very poor immunogen in mammals; this has been considered to be due to the induction of tolerance to cross-reactive host glycoconjugates. It has hampered the development of an effective vaccine against this meningococcal group for many years. Syngeneic populations have a similar tolerogenic background. Thus, we used the variability in ability to mount CpsB-specific immunoglobulin (Ig) responses of individuals from these populations to reveal underlying mechanisms to tolerance contributing to the poor immunogenicity of CpsB. Here we analyze by ELISA, the individual CpsB-specific Ig response of BALB/c and other syngeneic mice to immunization with intact bacteria, using the distribution of light chains as a direct indicator of the repertoire dynamics of the response. Although approximately 96% of anti-CpsB Ig bear kappa-light chains, BALB/c mouse populations were heterogeneous in the light chain composition of their individual anti-CpsB Ig responses. The proportion of kappa and lambda-light chains used for anti-CpsB Ig was a private characteristic that remained relatively constant, for each individual, through repetitive immunizations regardless of the bacterial stimuli size. Despite the prevalence of individual use of kappa-light chains, 5% of BALB/c mice showed restricted usage of lambda-light chains in their CpsB-specific Ig responses, and an additional 11% use them significantly. The preferential use of lambda-light chains in these mice was strongly associated with defective IgM, and absent or barely detectable IgG anti-CpsB responses even after repetitive bacterial immunization. We conclude that differences in the private repertoire of specific Ig also contribute to mouse unresponsiveness to CpsB.
Colino
Jesus
J
Department of Pathology, Uniformed Services Health Sciences University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. jcolino@usuhs.mil
Outschoorn
Ingrid
I
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000918:Antibody Specificity; D016667:Bacterial Capsules / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007114:Immunization; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007146:Immunoglobulin lambda-Chains / Q000097:blood*; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D009345:Neisseria meningitidis / Q000276:immunology*
D000907:Antibodies, Bacterial; D007147:Immunoglobulin Light Chains; D007146:Immunoglobulin lambda-Chains