Anthrax toxin effects on B lymphocyte function

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Title: Anthrax toxin effects on B lymphocyte function
Author: Bryan Thomas Gnade
Abstract: Bacillus anthracis is a gram -positive spore -forming rod capable of causing cutaneous , gastrointestinal and inhalational anthrax . It has a number of virulence factors of which , the two toxins are of great importance . Lethal toxin is a zinc metaloprotease that cleaves the N terminus of the mitogen -activated protein kinase (MAPK ) kinase family 1 -7 , with the exception of MEK5 . This kinase family is responsible for activating the mitogen -activated protein kinase (MAPK ) cascade . This cascade includes extracellular signal -regulated protein kinases (ERK ) , c -Jun NH2 -terminal kinases (JNK ) and p38 kinases . The disruption of these signaling pathways has a number of deleterious downstream effects that vary by cell type . Edema factor is a powerful calmodulin -dependent adenylyl cyclase that forms 3’ ,5’ -adenosine monophosphate (cAMP ) from adenosine triphosphate (ATP ) . This enzymatic reaction causes an increase in intracellular cyclic AMP (cAMP ) in host cells . As cAMP is a prominent second messenger in cellular signaling , edema toxin has a wide array of effects on numerous cell types and functions . \r \nTo determine the effects of the anthrax toxins on the adaptive immune response , B lymphocytes were exposed to LeTx or EdTx in vitro . LeTx and EdTx both inhibit B cell activation in different manners . LeTx inhibited B cell proliferation but not migration , while EdTx inhibited B cell migration but not proliferation . LeTx and EdTx altered expression patterns of B cell activation markers . EdTx inhibited MIP -1 & #945 ; and MIP -1 & #946 ; while enhancing IL -6 production . Previously unseen in any cell type EdTx was demonstrated to be cytotoxic to naïve B cells . \r \nThe research presented in this report illustrates the inhibitory effects of LeTx and EdTx on B lymphocytes , providing valuable insight into the immunoevasion tactics of B . anthracis . \r \n
URI: http : / /hdl .handle .net /2152 .3 /40
Date: 2010-01-11

Citation

Anthrax toxin effects on B lymphocyte function. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /40 .

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