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Title: THE ROLE OF B CELLS IN THE DEVELOPMENT OF CD4 EFFECTOR T CELLS DURING A POLARIZED TH2 IMMUNE RESPONSE.

Author
item LIU, QIAN - USUHS, BETHESDA, MD
item LIU, ZHUGONG - USUHS, BETHESDA, MD
item ROZO, CT - USUHS, BETHESDA MD
item HAMED, H.A - USUHS, BETHESDA MD
item VANNOY, JANSIE - USUHS, BETHESDA, MD
item Urban, Joseph
item GAUSE, W - USUHS, BETHESDA MD
item ALEM, F - USUHS, BETHESDA MD

Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/12/2007
Publication Date: 9/17/2007
Citation: Liu, Q., Liu, Z., Whitmire, J., Hossein, A., Vannoy, J., Urban Jr, J.F., Gause, W.C. 2007. The role of B cells in the development of CD4 effector T cells during a polarized TH2 immune response. Journal of Immunology. 179(6):3821-30.

Interpretive Summary: Immunity to nematode parasites is characterized by an ability to develop strong responses to that favor an immediate type hypersensitivity reaction that can expel worms from the intestine without severe effects on the equilibrium of the host. The molecular events that are necessary to trigger this response are not well understood, but they are critical for the production of appropriate vaccines against infectious agents or when the general health of the individual is affected by disease, nutrition, age or immune deficiency. The current study uses an experimental model of an infection with a gastrointestinal parasite that is injected into the skin to measure responses in the draining lymph nodes that regulate early development of the protein cytokine IL-4 that is a critical activator of the protective response to worm infection. The mice used were genetically deficient in a population of cells that helps in the production of IL-4, but the requirements for activation of these cells were not clearly defined. This report shows that whole proteins and not just small fragments of proteins are needed to activate these cells in order to initiate an optimal IL-4 response that is ultimately helpful in the clearance of worm parasites. This information will help develop on molecules that may be more important in stimulating responses to parasitic infections versus bacterial and viral agents and, thus, be more specific in action.

Technical Abstract: Several studies have suggested that B cells are essential for the development of IL-4 producing Th2 cells. To address this possibility in a highly polarized Th2 response, B cell deficient and wildtype BALB/c mice were infected with the intestinal nematode parasite, Nippostrongylus brasiliensis. No difference was detected in the development of either IL-4-producing cells in the mesenteric lymph node or CD4-dependent worm expulsion, indicating that B cells are not required for the development of a mucosal Th2 response and that Abs are not required for host protection. In contrast, the nonmucosal Th2 immune response to N. brasiliensis, examined in the draining lymph node following skin penetration, was reduced suggesting that the role of B cells in mediating Th2 cell differentiation differs depending on the tissue site. To examine the mechanism of T cell inhibition following parenteral inoculation, OVA-specific DO11.10 T cells were transferred to recipient mice, which were then inoculated intracutaneously in the ear with OVA + N. brasiliensis. Ag-specific Th2 cells development, migration, and cell cycle progression were partially inhibited. Reconstitution with untreated wildtype B cells restored Th2 cell IL-4 production when OVA peptide was used as the specific Ag and also cycle progression when OVA protein was used, suggesting that Ig cross-linking may be required.