J. Exp. Med., Volume 187, Number 6, March 16, 1998 929-937

Spontaneous Follicular Exclusion of SHP1-deficient B Cells Is Conditional on the Presence of Competitor Wild-type B Cells

By Kerstin N. Schmidt,^* Christopher W. Hsu,^* Courtney T. Griffin,^* Christopher C. Goodnow, and Jason G. Cyster^*

From the ^* Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California 94143; and the  Howard Hughes Medical Institute, Beckman Center, Stanford University School of Medicine, Stanford, California 94305

Engagement of antigen receptors on mature B lymphocytes is known to block cell entry into lymphoid follicles and promote accumulation in T cell zones, yet the molecular basis for this change in cell distribution is not understood. Previous studies have shown that follicular exclusion requires a threshold level of antigen receptor engagement combined with occupancy of follicles by B cells without equivalent receptor engagement. The possibility has been raised that follicular composition affects B cell positioning by altering the amount of available antigen and the degree of receptor occupancy. Here we show that follicular composition affects migration of mature B cells under conditions that are independent of antigen receptor occupancy. B cells deficient in the negative regulatory protein tyrosine phosphatase, SHP1, which have elevated intracellular signaling by the B cell receptor, are shown to accumulate in the T zone in the absence of their specific antigen. Follicular exclusion of SHP1-deficient B cells was found to be conditional on the presence of excess B cells that lack elevated intracellular signaling, and was not due to a failure of SHP-1-deficient cells to mature and express the follicle-homing chemokine receptor Burkitt's lymphoma receptor 1. These findings strongly suggest that signals that are negatively regulated by SHP1 promote B cell localization in T cell zones by reducing competitiveness for follicular entry, and provide further evidence that follicular composition influences the positioning of antigen-engaged B cells.

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