Isotype-specific Selection of High Affinity Memory B Cells in Nasal-associated Lymphoid Tissue

Abstract

Mucosal immunoglobulin (Ig)A dominance has been proposed to be associated with preferential class switch recombination (CSR) to the IgA heavy chain constant region, Cα. Here, we report that B cell activation in nasal-associated lymphoid tissue (NALT) upon stimulation with the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to chicken γ globulin caused an anti-NP memory response dominated by high affinity IgA antibodies. In the response, however, NP-specific IgG+ B cells expanded and sustained their number as a major population in germinal centers (GCs), supporting the view that CSR to IgG heavy chain constant region, Cγ, operated efficiently in NALT. Both IgG+ and IgA+ GC B cells accumulated somatic mutations, indicative of affinity maturation to a similar extent, suggesting that both types of cell were equally selected by antigen. Despite the selection in GCs, high affinity NP-specific B cells were barely detected in the IgG memory compartment, whereas such cells dominated the IgA memory compartment. Taken together with the analysis of the VH gene clonotype in GC and memory B cells, we propose that NALT is equipped with a unique machinery providing IgA-specific enrichment of high affinity cells into the memory compartment, facilitating immunity with high affinity and noninflammatory secretory antibodies.

Distribution and phenotype of murine rotavirus-specific B cells induced by intranasal immunization with 2/6 virus-like particles

“…In a general manner, RV-specific B cells, remained detectable for 3 months in both NALT and CLN, in contrast to results reported by Shimoda et al [18] with an hapten model, which showed a rapid decrease of the hapten-specific B cell response in NALT, between 13 and 20 days after i.n. immunization of C57BL/6 mice.…”

“…immunization of C57BL/6 mice. A sustained B cell response has also been observed after oral administration of live RV by Youngman et al [15], who have suggested that viral Ag organization may explain the differences observed between the hapten and the viral model [18]. Nevertheless, here, although memory RV-specific B cells were still detected at 3 months, we did not observe an accumulation of long-term memory RV-specific B cell response in NALT after one immunization as shown in PP after oral inoculation [15].…”

“…Three types of RV-specific B220 + cells were identified as illustrated in Fig. 2 [15,17,18]. We also analyzed large B220 -cells to not exclude plasmablasts.…”

Local and Systemic Antibody Responses in Mice Immunized Intranasally with Native and Detergent-Extracted Outer Membrane Vesicles fromNeisseria meningitidis

“…Mucosal B cells seem to have a preference for immunoglobulin class switch recombination from to ␣, probably through stimulation with transforming growth factor ␤, interleukin-10, and CD40, as indicated by a number of in vitro studies (13,18,33,40,50). The mechanism for preferential class switching to IgA is not fully understood, but the O-NALT was recently proposed to possess a unique machinery that provides an enrichment of high-affinity IgA-but not IgG-specific cells in the memory compartment (45). The same study also showed that the frequency of IgG2b-expressing cells in the O-NALT which peaked at day 7 and persisted up to day 11, was about three to four times the number of IgA-producing cells (45).…”

“…The mechanism for preferential class switching to IgA is not fully understood, but the O-NALT was recently proposed to possess a unique machinery that provides an enrichment of high-affinity IgA-but not IgG-specific cells in the memory compartment (45). The same study also showed that the frequency of IgG2b-expressing cells in the O-NALT which peaked at day 7 and persisted up to day 11, was about three to four times the number of IgA-producing cells (45). In contrast, our study showed that either only IgA-producing AFCs or equal numbers of IgA-and IgG2b-producing AFCs, were found in the O-NALT on day 11 or 12, and no specific AFCs were detected on day 30 or 33.…”