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T cell-independent Abs are protective against Lyme disease and relapsing fever, illnesses caused by Borrelia spirochetes with distinct blood-borne phases of infection. To understand this protective response, we characterized splenic and peritoneal B cell compartments during infection using flow cytometry and immunohistochemistry. In the spleen, early after infection, Borrelia crocidurae, a relapsing fever species, induced a striking loss of marginal zone (MZ) B cells from the MZ, while Borrelia burgdorferi, the agent of Lyme disease, induced the expansion of this subset. At the same time, no significant changes were observed in follicular B cells in response to either species of Borrelia. In the peritoneal cavity, a further loss was demonstrated early in response to B. crocidurae in the B1b, B1c, and B2 cell subsets, but B1a cells were not significantly altered. The loss of B1c and B2 cells was sustained through subsequent peaks of spirochetemia, suggesting these subsets may be important in resolving relapsing episodes. In contrast, an early and significant increase in peritoneal B1a, B1b, and B1c cells, but not B2 cells, occurred in response to B. burgdorferi. Later in the course of infection, both species of Borrelia induced the selective expansion of peritoneal B1b cells, suggesting that B1b cells may participate in long-lasting immunity to Lyme and relapsing fever spirochetes. Our data demonstrate that different Borrelia can activate the same B cell subsets in distinct ways and they each elicit a complex interplay of MZ and multiple peritoneal B cell subsets in the early response to infection.

T cells constitute the pathogenic effector cell population in autoimmune myocarditis in BALB/c mice. Using mice rendered deficient for B cells by a targeted disruption to the IgM transmembrane domain or by treatment with anti-IgM Ab from birth, we asked whether B cells are a critical APC in the induction of autoimmune myocarditis. B cell-deficient mice immunized with cardiac myosin develop myocarditis comparable in incidence and severity to that in wild-type mice, suggesting that autoreactive T cells that cause myocarditis in BALB/c mice are activated by macrophages or dendritic cells. Since it does not appear that presentation of cryptic epitopes is critical for the breakdown of self tolerance, potentially pathogenic T cells recognizing dominant myosin epitopes must have escaped tolerization. Either anatomic sequestration of cardiac myosin peptide-MHC complexes or subthreshold presentation of cardiac myosin peptides by conventional APC can explain the survival of these autoreactive T cells.