The Journal of Experimental Medicine
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Published online 28 December 2004 doi:10.1084/jem.20041849
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 1, 55-62
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ARTICLE

Positive selection of the peripheral B cell repertoire in gut-associated lymphoid tissues

Ki-Jong Rhee, Paul J. Jasper, Periannan Sethupathi, Malathy Shanmugam, Dennis Lanning, and Katherine L. Knight

Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153

CORRESPONDENCE Katherine L. Knight: kknight{at}lumc.edu

Gut-associated lymphoid tissues (GALTs) interact with intestinal microflora to drive GALT development and diversify the primary antibody repertoire; however, the molecular mechanisms that link these events remain elusive. Alicia rabbits provide an excellent model to investigate the relationship between GALT, intestinal microflora, and modulation of the antibody repertoire. Most B cells in neonatal Alicia rabbits express VHn allotype immunoglobulin (Ig)M. Within weeks, the number of VHn B cells decreases, whereas VHa allotype B cells increase in number and become predominant. We hypothesized that the repertoire shift from VHn to VHa B cells results from interactions between GALT and intestinal microflora. To test this hypothesis, we surgically removed organized GALT from newborn Alicia pups and ligated the appendix to sequester it from intestinal microflora. Flow cytometry and nucleotide sequence analyses revealed that the VHn to VHa repertoire shift did not occur, demonstrating the requirement for interactions between GALT and intestinal microflora in the selective expansion of VHa B cells. By comparing amino acid sequences of VHn and VHa Ig, we identified a putative VH ligand binding site for a bacterial or endogenous B cell superantigen. We propose that interaction of such a superantigen with VHa B cells results in their selective expansion.


Abbreviations used: BCR, B cell receptor; FR, framework region; GALT, gut-associated lymphoid tissue; LigApx, ligated appendix.

K.-J. Rhee and P.J. Jasper contributed equally to this work.


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