VHJ558 transgenic mice: A model to study the development of polysaccharide specific B cells and the antibody response to gram‐negative bacteria

To investigate development of the antibody response to α 1→3‐dextran (DEX), expressed by Enterobacter cloacae , we made transgenic mice expressing a V H J558.3‐DSP2.2‐J H 1 heavy chain (TG) that pairs with λ1 light chains to generate specificity for DEX (DEX+). DEX+ B cells, identified with anti‐idiotypic reagents, enrich in MZ and B1b B cell subsets in a B cell receptor dependent process. TG mice immunized intravenously (IV) with E. cloacae generate a DEX specific antibody response, which peaks at 3 days and persists at 10% of peak titers for 28 days before returning to preimmune levels. Analysis of DEX+ plasma cell kinetics by Brdu incorporation indicated that persistent antibody titers were maintained through de novo plasma cell generation. After immunization, B lymphopoiesis is temporarily abolished and DEX specific B cell production curtailed, yet, DEX specific B cells begin repopulating the MZ niche a week after their initial depletion in a manner that appears to be the result of DEX induced peripheral B cell clonal expansion. This model provides an example of selection of carbohydrate specific B cells into the MZ and B1b B cell subsets and illustrates the rapid, persistent nature of DEX specific antibody production. Furthermore, repopulation of the MZ by DEX+ B cells in the temporary absence of B lymphopoiesis indicates a role for peripheral B cells in the reconstitution of this niche.