Heterogeneity of the BALB/c antiphosphorylcholine antibody response at the precursor cell level

doi:10.1084/jem.141.1.56

This Article

	Full Text (PDF, 1058K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Gearhart, P. J.
	Articles by Klinman, N. R.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Gearhart, P. J.
	Articles by Klinman, N. R.


Social Bookmarking

	What's this?

ARTICLES

Heterogeneity of the BALB/c antiphosphorylcholine antibody response at the precursor cell level

PJ Gearhart, NH Sigal and NR Klinman

Immune responsiveness to phosphorylcholine (PC) in BALB/c mice has been characterized by combining (a) usuage of highly sensitive radioimmunoassays for quantitation of antibody, heavy-chain class, and idiotype on a weight basis; (b) isolation of PC-specific B cells in fragment cultures; and (c) stimulation in a carrier-primed environment with the PC hapten coupled to carrier through a tripeptide spacer in order to maximize carrier recognition. The specificity and accuracy of the radioimmunoassays have veen verified by specific inhibition, lack of nonspecific binding, and excellent concordance of values for monoclonal antibody concentration obtained independently for Fab and idiotype content. The latter evidence also serves as strong confirmation of the monoclonality of in vitro monofocal responses as well as the preservation of the idiotype on antibodies of differing immunoglobulin classes. The results indicate that while B cells expressing the TEPC 15 idiotype predominate, other idiotypes may be represented by 2-50% of PC-specific precursors, and monoclonal antibodies even of the TEPC 15 idiotype are produced in both the IgM and IgG1 immunoglobulin classes. These findings are confirmed by the analysis of serum antibodies produced in carrier-primed mice immunized with hapten coupled through a tripeptide spacer, thus re-emphasizint the enhancement of primary responsiveness, particularly IgG1 production, by maximizing carrier recognition. The finding of idiotype diversity in the PC response, as well as diversity of expression in terms of quantity and immunoglobulin class of antibody synthesized by the clonal progeny of B cells within the TEPC 15 clonotype, emphasize the heterogeneity of the B-cell population both in terms of specificity repertoire and the physiological state of cells even within a single clonotype.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Thomas-Rudolph, D., Du Clos, T. W., Snapper, C. M., Mold, C. (2007). C-Reactive Protein Enhances Immunity to Streptococcus pneumoniae by Targeting Uptake to Fc{gamma}R on Dendritic Cells. J. Immunol. 178: 7283-7291 [Abstract] [Full Text]
Bang, R., Marnell, L., Mold, C., Stein, M.-P., Clos, K. T. D., Chivington-Buck, C., Clos, T. W. D. (2005). Analysis of Binding Sites in Human C-reactive Protein for Fc{gamma}RI, Fc{gamma}RIIA, and C1q by Site-directed Mutagenesis. J. Biol. Chem. 280: 25095-25102 [Abstract] [Full Text]
Hu, L., Rezanka, L. J., Mi, Q.-S., Lustig, A., Taub, D. D., Longo, D. L., Kenny, J. J. (2002). T15-Idiotype-Negative B Cells Dominate the Phosphocholine Binding Cells in the Preimmune Repertoire of T15i Knockin Mice. J. Immunol. 168: 1273-1280 [Abstract] [Full Text]
Alfonso, C., Han, J.-O., Williams, G. S., Karlsson, L. (2001). The Impact of H2-DM on Humoral Immune Responses. J. Immunol. 167: 6348-6355 [Abstract] [Full Text]
Klinman, N. R., Sigal, N. H., Metcalf, E. S., Pierce, S. K., Gearhart, P. J. (1977). The Interplay of Evolution and Environment in B-cell Diversification. Cold Spring Harb Symp Quant Biol 41: 165-173 [Abstract]
Cebra, J. J., Gearhart, P. J., Kamat, R., Robertson, S. M., Tseng, J. (1977). Origin and Differentiation of Lymphocytes Involved in the Secretory IgA Response. Cold Spring Harb Symp Quant Biol 41: 201-215 [Abstract]
Cosenza, H., Augustin, A. A., Julius, M. H. (1977). Idiotypes and Anti-idiotypes as Probes in Analysis of Immunoregulation. Cold Spring Harb Symp Quant Biol 41: 709-718 [Abstract]
Claflin, J. L., Rudikoff, S. (1977). Uniformity in a Clonal Repertoire: A Case for a Germ-line Basis of Antibody Diversity. Cold Spring Harb Symp Quant Biol 41: 725-734 [Abstract]