Development of Immunoglobulin M Memory to Both a T-Cell-Independent and a T-Cell-Dependent Antigen following Infection withVibrio choleraeO1 in Bangladesh

Abstract

Vibrio cholerae O1 can cause severe watery diarrhea that can be life-threatening without treatment. Infection results in long-lasting protection against subsequent disease. Development of memory B cells of the immunoglobulin G (IgG) and IgA isotypes to V. cholerae O1 antigens, including serotype-specific lipopolysaccharide (LPS) and the B subunit of cholera toxin (CTB), after cholera infection has been demonstrated. Memory B cells of the IgM isotype may play a role in long-term protection, particularly against T-cell-independent antigens, but IgM memory has not been studied in V. cholerae O1 infection. Therefore, we assayed acute-and convalescent-phase blood samples from cholera patients for the presence of memory B cells that produce cholera antigen-specific IgM antibody upon polyclonal stimulation in in vitro culture. We also examined the development of serological and antibody-secreting cell responses following infection. Subjects developed significant IgM memory responses by day 30 after infection, both to the T-cell-independent antigen LPS and to the T-cell-dependent antigen CTB. No significant corresponding elevations in plasma IgM antibodies or circulating IgM antibody-secreting cells to CTB were detected. In 17 subjects followed to day 90 after infection, significant persistence of elevated IgM memory responses was not observed. The IgM memory response to CTB was negatively correlated with the IgG plasma antibody response to CTB, and there was a trend toward negative correlation between the IgM memory and IgA plasma antibody responses to LPS. We did not observe an association between the IgM memory response to LPS and the vibriocidal titer.

Comparison of Memory B Cell, Antibody-Secreting Cell, and Plasma Antibody Responses in Young Children, Older Children, and Adults with Infection Caused by Vibrio cholerae O1 El Tor Ogawa in Bangladesh

“…Baseline IgM responses to LPS in children were significantly higher than those in adults, which is opposite what was observed for vibriocidal antibody. Despite the fact that the vibriocidal antibody is mostly IgM directed to LPS (23,25), we have previously observed that no correlation exists between plasma IgM and vibriocidal antibodies in adults with cholera (18). The LPS-specific IgA response in adults was higher than that in young children on day 30; this observation may reflect the ability of adults to mount more-prominent immune responses to T cell-independent antigens than young children (19).…”

Differential compartmentalization of memory B cells versus plasma cells in salmonid fish

“…First, the kinetics, magnitude, and affinity of the TI and TD responses were quite similar. Both responses exhibited a relatively short primary phase versus a prolonged secondary and both maintained the high affinity achieved late in the primary (by week 16), even as the titers began to wane (week [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. This heightened affinity continued into the secondary, with even a slight increase (∼from −log aK 5.9 to 6.2), late in the secondary.…”

“…Intriguingly, characteristics of teleost memory B cells (MBCs) [9] parallel those associated with a class of mammalian MBCs. Recent evidence reveals that human MBCs can include unswitched, mutated IgM + cells [23]; nonmutated, CD27 + IgM + cells [24], those induced by T-independent (TI) antigens [25,26], preimmune diversified repertoires [27] (as has recently been posed for the catfish [19]), or arise independently of GCs [27,28]. Together, these previous studies prompt a renewed focus on the critical elements of μ specific memory, both in teleosts and mammals.…”

Antigen-Specific Memory B-Cell Responses in Bangladeshi Adults after One- or Two-Dose Oral Killed Cholera Vaccination and Comparison with Responses in Patients with Naturally Acquired Cholera

“…We compared immune responses following WC-rBS vaccination to those occurring following natural cholera in 70 adult cholera patients (male, n ϭ 38; female, n ϭ 32) (8,16,37). Adult patients presenting with severe, acute watery diarrhea who had a positive stool culture for V. cholerae O1 and were without significant comorbid conditions were eligible for inclusion in the study.…”