The response of B cells in spleen, Peyer's patches, and lymph nodes to LPS and IL-4.
The vast majority of B lymphocytes in the Peyer's patches (PP) and lymph nodes (LN) are memory cells or activated cells. Hence, in comparison to B lymphocytes in the spleen (SP), most B cells in these lymphoid organs have already encountered antigen. To further examine the ability of B cells in these peripheral lymphoid organs to respond to mitogens and interleukins in vitro, we have analyzed the ability of these cells (as compared to splenic B cells) to respond to LPS and LPS plus IL-4. Our results indicate that B cells from PPs and LNs proliferate poorly to LPS during the first 3 days of culture. In contrast, at later times, PP and LN B cells show enhanced proliferation as compared to splenic B cells. Furthermore, the addition of Interleukin-4 (IL-4) changes the proliferative activity of B cells from PPs and LNs, had only a minimal effect on splenic B cells. Hence, high doses of IL-4 (100 units/ml) enhance the proliferative rate of B cells from PPs and LNs early after activation, and have a suppressive effect at later times. The enhanced response of cells in PPs and LNs is further manifested by the presence of larger numbers of sIgG1+ cells 4 days after activation with LPS plus IL-4 and at 5 days these cells also secrete proportionally more IgG1 than splenic B cells. Enhanced IgG1 secretion is reflected in the methylation pattern of the s gamma 1 switch region of these cells. In cells from PP and LN cultured with LPS plus IL-4, most alleles containing the s gamma 1 region are demethylated or partly deleted, reflecting activation of this region of the Ig gene complex. In contrast, in splenic B cells, half the alleles remain in germline configuration. Our results suggest the presence of larger numbers of "preactivated" B cells in PPs and LNs as compared to spleen. These cells more rapidly secrete Ig following stimulation with LPS plus IL-4 in the absence of significant proliferation.
Burger
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Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Vitetta
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D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000276:immunology*; D013154:Spleen / Q000276:immunology*
D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D015847:Interleukin-4